Platelet COX and LOX enzymes orchestrate amyloid-β secretion via RhoA signaling: Implications for neurodegenerative diseases

Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process im...

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Vydáno v:	Free radical biology & medicine Ročník 240; s. 641 - 649
Hlavní autoři:	Trostchansky, A., Alarcón, M.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 01.12.2025
Témata:	Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer Disease - pathology Amyloid beta-Peptides - genetics Amyloid beta-Peptides - metabolism Amyloid-β Arachidonate 12-Lipoxygenase - genetics Arachidonate 12-Lipoxygenase - metabolism Blood Platelets - enzymology Blood Platelets - metabolism Cerebral Amyloid Angiopathy - genetics Cerebral Amyloid Angiopathy - metabolism Cerebral Amyloid Angiopathy - pathology Cyclooxygenase Cyclooxygenase 1 - genetics Cyclooxygenase 1 - metabolism Humans Lipoxygenase Peptide Fragments - metabolism Platelet Activation Platelets rhoA GTP-Binding Protein - genetics rhoA GTP-Binding Protein - metabolism Signal Transduction Cyclooxygenase Amyloid-β Lipoxygenase Platelets
ISSN:	0891-5849, 1873-4596, 1873-4596
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Abstract	Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Using an integrative approach combining bioinformatic protein–protein interaction mapping, pathway enrichment analysis, and experimental validation, we identified extensive networks linking PTGS and ALOX isoforms to cytoskeletal remodeling, mitochondrial function, and vesicle trafficking. Functional enrichment pointed to key roles for PTGS1 and ALOX12 in platelet activation and secretory processes. In vitro studies demonstrated that stimulation of human platelets with TRAP-6 triggered a robust increase in Aβ40 secretion, which was significantly attenuated by COX inhibition or blockade of RhoA, a critical regulator of cytoskeletal dynamics. These findings suggest that platelet-derived Aβ release is driven by COX/LOX-dependent signaling via RhoA. While our results support a COX/LOX-RhoA axis, we recognize that causality remains to be fully established, and the role of ALOX12 requires further experimental validation. Given the vascular deposition of Aβ40 in CAA, our results position platelets as important peripheral contributors to neurovascular amyloidosis. This study should therefore be viewed as hypothesis-generating, underscoring the therapeutic potential of targeting platelet signaling pathways to mitigate Aβ-driven vascular pathology. [Display omitted] •Novel PTGS1–ALOX12–RhoA pathway regulates amyloid-β40 release from activated platelets.•Platelets are key sources of Aβ40, amplifying cerebral amyloid angiopathy and Alzheimer’s disease pathology.•Targeting the platelet COX/LOX–RhoA axis may reduce vascular amyloid deposition and slow. neurodegenerative progression.
AbstractList	Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Using an integrative approach combining bioinformatic protein-protein interaction mapping, pathway enrichment analysis, and experimental validation, we identified extensive networks linking PTGS and ALOX isoforms to cytoskeletal remodeling, mitochondrial function, and vesicle trafficking. Functional enrichment pointed to key roles for PTGS1 and ALOX12 in platelet activation and secretory processes. In vitro studies demonstrated that stimulation of human platelets with TRAP-6 triggered a robust increase in Aβ40 secretion, which was significantly attenuated by COX inhibition or blockade of RhoA, a critical regulator of cytoskeletal dynamics. These findings suggest that platelet-derived Aβ release is driven by COX/LOX-dependent signaling via RhoA. While our results support a COX/LOX-RhoA axis, we recognize that causality remains to be fully established, and the role of ALOX12 requires further experimental validation. Given the vascular deposition of Aβ40 in CAA, our results position platelets as important peripheral contributors to neurovascular amyloidosis. This study should therefore be viewed as hypothesis-generating, underscoring the therapeutic potential of targeting platelet signaling pathways to mitigate Aβ-driven vascular pathology. Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Using an integrative approach combining bioinformatic protein-protein interaction mapping, pathway enrichment analysis, and experimental validation, we identified extensive networks linking PTGS and ALOX isoforms to cytoskeletal remodeling, mitochondrial function, and vesicle trafficking. Functional enrichment pointed to key roles for PTGS1 and ALOX12 in platelet activation and secretory processes. In vitro studies demonstrated that stimulation of human platelets with TRAP-6 triggered a robust increase in Aβ40 secretion, which was significantly attenuated by COX inhibition or blockade of RhoA, a critical regulator of cytoskeletal dynamics. These findings suggest that platelet-derived Aβ release is driven by COX/LOX-dependent signaling via RhoA. While our results support a COX/LOX-RhoA axis, we recognize that causality remains to be fully established, and the role of ALOX12 requires further experimental validation. Given the vascular deposition of Aβ40 in CAA, our results position platelets as important peripheral contributors to neurovascular amyloidosis. This study should therefore be viewed as hypothesis-generating, underscoring the therapeutic potential of targeting platelet signaling pathways to mitigate Aβ-driven vascular pathology.Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Using an integrative approach combining bioinformatic protein-protein interaction mapping, pathway enrichment analysis, and experimental validation, we identified extensive networks linking PTGS and ALOX isoforms to cytoskeletal remodeling, mitochondrial function, and vesicle trafficking. Functional enrichment pointed to key roles for PTGS1 and ALOX12 in platelet activation and secretory processes. In vitro studies demonstrated that stimulation of human platelets with TRAP-6 triggered a robust increase in Aβ40 secretion, which was significantly attenuated by COX inhibition or blockade of RhoA, a critical regulator of cytoskeletal dynamics. These findings suggest that platelet-derived Aβ release is driven by COX/LOX-dependent signaling via RhoA. While our results support a COX/LOX-RhoA axis, we recognize that causality remains to be fully established, and the role of ALOX12 requires further experimental validation. Given the vascular deposition of Aβ40 in CAA, our results position platelets as important peripheral contributors to neurovascular amyloidosis. This study should therefore be viewed as hypothesis-generating, underscoring the therapeutic potential of targeting platelet signaling pathways to mitigate Aβ-driven vascular pathology. Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Using an integrative approach combining bioinformatic protein–protein interaction mapping, pathway enrichment analysis, and experimental validation, we identified extensive networks linking PTGS and ALOX isoforms to cytoskeletal remodeling, mitochondrial function, and vesicle trafficking. Functional enrichment pointed to key roles for PTGS1 and ALOX12 in platelet activation and secretory processes. In vitro studies demonstrated that stimulation of human platelets with TRAP-6 triggered a robust increase in Aβ40 secretion, which was significantly attenuated by COX inhibition or blockade of RhoA, a critical regulator of cytoskeletal dynamics. These findings suggest that platelet-derived Aβ release is driven by COX/LOX-dependent signaling via RhoA. While our results support a COX/LOX-RhoA axis, we recognize that causality remains to be fully established, and the role of ALOX12 requires further experimental validation. Given the vascular deposition of Aβ40 in CAA, our results position platelets as important peripheral contributors to neurovascular amyloidosis. This study should therefore be viewed as hypothesis-generating, underscoring the therapeutic potential of targeting platelet signaling pathways to mitigate Aβ-driven vascular pathology. [Display omitted] •Novel PTGS1–ALOX12–RhoA pathway regulates amyloid-β40 release from activated platelets.•Platelets are key sources of Aβ40, amplifying cerebral amyloid angiopathy and Alzheimer’s disease pathology.•Targeting the platelet COX/LOX–RhoA axis may reduce vascular amyloid deposition and slow. neurodegenerative progression.
Author	Trostchansky, A. Alarcón, M.
Author_xml	– sequence: 1 givenname: A. orcidid: 0000-0002-9721-7577 surname: Trostchansky fullname: Trostchansky, A. email: trocha@fmed.edu.uy organization: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, 11800, Uruguay – sequence: 2 givenname: M. surname: Alarcón fullname: Alarcón, M. email: malarcon@utalca.cl organization: Thrombosis Research Center, Universidad de Talca, Talca, 3460000, Chile
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Cites_doi	10.1016/j.gene.2015.07.073 10.1111/jnc.12059 10.1007/s11064-015-1776-x 10.1038/nchem.247 10.1093/cvr/cvab003 10.1016/j.chembiol.2012.05.009 10.1016/j.bbalip.2014.10.008 10.1038/sj.onc.1203286 10.3390/ijms25073961 10.2174/1567205015666180404165915 10.1002/pro.3978 10.1016/j.bbalip.2018.03.005 10.1358/mf.2000.22.5.796648 10.5041/RMMJ.10426 10.1186/s12950-014-0033-4 10.1182/blood-2011-10-387308 10.1093/nar/gkt1115 10.1194/jlr.R800042-JLR200 10.3389/fphar.2024.1520488 10.1016/S0021-9258(18)55493-4 10.1038/s41582-019-0281-2 10.1146/annurev.med.53.082901.103952 10.1161/ATVBAHA.123.319021 10.3390/ijms24044167 10.1038/srep11086 10.3233/JAD-2002-4309 10.3390/cells8070689 10.1155/2019/2749173 10.2174/1871527320666210208130412 10.3324/haematol.2019.223529 10.1016/j.prostaglandins.2021.106607 10.1074/jbc.M307699200 10.1093/nar/gkv1115 10.1016/j.plipres.2018.11.001 10.1021/acs.chemrev.0c00215 10.1016/j.ijbiomac.2020.10.270 10.1182/blood.2021013097 10.1046/j.1440-1789.2000.00268.x 10.1055/s-0035-1564835 10.3233/JAD-131223 10.3389/fnmol.2022.927530 10.1002/ana.22234 10.1186/s12859-017-1934-z 10.1016/j.ejphar.2015.08.049 10.1186/gb-2004-5-9-241 10.2174/187152511797037619 10.1002/ana.21694 10.1016/j.pharmthera.2023.108420 10.1212/01.WNL.0000106953.49802.9C 10.1016/j.neuroscience.2018.11.025 10.1093/database/baz005 10.1093/bioinformatics/btz931 10.1006/bbrc.1995.2103 10.1016/j.molcel.2018.11.035 10.1089/ars.2011.3895 10.1016/j.redox.2015.08.006 10.4168/aair.2021.13.5.684
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References	Greenberg, Bacskai, Hernandez-Guillamon, Pruzin, Sperling, van Veluw (bib18) 2020; 16 Rouzer, Marnett (bib34) 2009; 50 Sun, Zhou, Mao (bib9) 2019; 2019 Orre, Vesterlund, Pan, Arslan, Zhu, Fernandez Woodbridge, Frings, Fredlund, Lehtiö (bib46) 2019; 73 Sepulveda, Hernandez, Burgos, Fuentes, Palomo, Alarcon (bib28) 2019; 397 Boyanova, Nilla, Birschmann, Dandekar, Dittrich (bib44) 2012; 119 Maskrey, Rushworth, Law, Treweeke, Wei, Leslie, Megson, Whitfield (bib56) 2014; 11 Turnbull, Sander, Turnbull, Barrett, Goodall (bib59) 2022; 158 Poorani, Bhatt, Dwarakanath, Das (bib57) 2016; 785 Alonso-López, Campos-Laborie, Gutiérrez, Lambourne, Calderwood, Vidal, De Las Rivas (bib42) 2019; 2019 Stanger, Holinstat (bib58) 2023; 246 Bernstein, Dupuis, Lazo, Wyttenbach, Condron, Bitan, Teplow, Shea, Ruotolo, Robinson, Bowers (bib17) 2009; 1 Badimon, Vilahur, Rocca, Patrono (bib1) 2021; 117 Kulkarni, Jain, Singh (bib7) 2000; 22 Chandrasekharan, Simmons (bib14) 2004; 5 Berra-Romani, Faris, Negri, Botta, Genova, Moccia (bib2) 2019; 8 Choi, Aid, Caracciolo, Minami, Niikura, Matsuoka, Turner, Mattson, Bosetti (bib37) 2013; 124 Yamada (bib21) 2000; 20 Contursi, Tacconelli, Di Berardino, De Michele, Patrignani (bib53) 2024; 15 Shankar Sharma, Botta, Tsai, Holman, Holinstat (bib60) 2023; 142 Xu, Li, Zhang, Zhang (bib12) 2021; 13 Butterfield, Griffin, Munch, Pasinetti (bib22) 2002; 4 Powell, Rokach (bib11) 2015; 1851 Yeung, Holinstat (bib33) 2011; 9 Czapski, Czubowicz, Strosznajder, Strosznajder (bib15) 2016; 41 Epis, Marcello, Gardoni, Di Luca (bib24) 2012; 4 Chu, Li, Hoffman, Stough, Madesh, Pratico (bib30) 2015; 5 Gorica, Calderone (bib4) 2022; 21 Faki, Er (bib6) 2021; 12 Bush, Martins, Rumble, Moir, Fuller, Milward, Currie, Ames, Weidemann, Fischer (bib36) 1990; 265 Mukaetova-Ladinska, Abdell-All, Andrade, da Silva, Boksha, Burbaeva, Kalaria, J (bib27) 2018; 15 Dandamudi, Seibel, Tourdot, Cancelas, Akbar, Zheng (bib49) 2023; 24 Shang, Marchioni, Sipes, Evelyn, Jerabek-Willemsen, Duhr, Seibel, Wortman, Zheng (bib50) 2012; 19 Orchard, Ammari, Aranda, Breuza, Briganti, Broackes-Carter, Campbell, Chavali, Chen, del-Toro, Duesbury, Dumousseau, Galeota, Hinz, Iannuccelli, Jagannathan, Jimenez, Khadake, Lagreid, Licata, Lovering, Meldal, Melidoni, Milagros, Peluso, Perfetto, Porras, Raghunath, Ricard-Blum, Roechert, Stutz, Tognolli, van Roey, Cesareni, Hermjakob (bib40) 2013; 42 Yang, Li, Li, Ma, Hou, Zhou, Zhou (bib19) 2022; 15 Amoah, Pestov, Korneenko, Prokhorenko, Kurakin, Barlev (bib13) 2024; 25 Lagarde, Guichardant, Bernoud-Hubac, Calzada, Vericel (bib54) 2018; 1863 Ge, Jung, Yao (bib45) 2020; 36 Ivanov, Kuhn, Heydeck (bib8) 2015; 573 Qin, Ho, Pompl, Peng, Zhao, Xiang, Robakis, Shioi, Suh, Pasinetti (bib39) 2003; 278 Verbeek, Kremer, Rikkert, Van Domburg, Skehan, Greenberg (bib20) 2009; 66 Mashima, Okuyama (bib32) 2015; 6 Rueden, Schindelin, Hiner, DeZonia, Walter, Arena, Eliceiri (bib48) 2017; 18 Oughtred, Rust, Chang, Breitkreutz, Stark, Willems, Boucher, Leung, Kolas, Zhang, Dolma, Coulombe-Huntington, Chatr-aryamontri, Dolinski, Tyers (bib43) 2021; 30 Larsen, Byrne, Ozpolat, Chauhan, Bailey, Rhoads, Reed, Stolla, Adili, Holinstat, Fu, Stolla (bib55) 2023; 43 Singh, Rao (bib16) 2019; 73 Gremmel, Frelinger, Michelson (bib31) 2016; 42 Unsworth, Bye, Sage, Gaspar, Eaton, Drew, Stainer, Kriek, Volberding, Hutchinson, Riley, Jones, Mundell, Cui, Falet, Gibbins (bib51) 2021; 106 Ghiso, Tomidokoro, Révész, Frangione, Rostagno (bib61) 2010; 61 Williams, Mann, DuBois (bib10) 1999; 18 Recabarren-Leiva, Burgos, Hernández, Garcïa-García, Castro, Guzman, Fuentes, Palomo, Alarcón (bib47) 2021; 166 Calder (bib3) 2020 Joshi, Di Meco, Pratico (bib25) 2014; 38 Chu, Pratico (bib38) 2011; 69 Carrano, Hoozemans, van der Vies, Rozemuller, van Horssen, de Vries (bib23) 2011; 15 Chen, Inestrosa, Ross, Fernandez (bib29) 1995; 213 Rouzer, Marnett (bib35) 2020; 120 Cebo, Dittrich, Fu, Manke, Emschermann, Rheinlaender, von Eysmondt, Ferreiros, Sudman, Witte, Pelzl, Borst, Geisler, Rath, Bakchoul, Gawaz, Schaffer, Lammerhofer, Chatterjee (bib52) 2022; 139 Kotlyar, Pastrello, Sheahan, Jurisica (bib41) 2015; 44 Turini, DuBois (bib5) 2002; 53 Colciaghi, Marcello, Borroni, Zimmermann, Caltagirone, Cattabeni, Padovani, Di Luca (bib26) 2004; 62 Sun (10.1016/j.freeradbiomed.2025.08.060_bib9) 2019; 2019 Joshi (10.1016/j.freeradbiomed.2025.08.060_bib25) 2014; 38 Orchard (10.1016/j.freeradbiomed.2025.08.060_bib40) 2013; 42 Shang (10.1016/j.freeradbiomed.2025.08.060_bib50) 2012; 19 Boyanova (10.1016/j.freeradbiomed.2025.08.060_bib44) 2012; 119 Xu (10.1016/j.freeradbiomed.2025.08.060_bib12) 2021; 13 Contursi (10.1016/j.freeradbiomed.2025.08.060_bib53) 2024; 15 Berra-Romani (10.1016/j.freeradbiomed.2025.08.060_bib2) 2019; 8 Ge (10.1016/j.freeradbiomed.2025.08.060_bib45) 2020; 36 Butterfield (10.1016/j.freeradbiomed.2025.08.060_bib22) 2002; 4 Mukaetova-Ladinska (10.1016/j.freeradbiomed.2025.08.060_bib27) 2018; 15 Kotlyar (10.1016/j.freeradbiomed.2025.08.060_bib41) 2015; 44 Sepulveda (10.1016/j.freeradbiomed.2025.08.060_bib28) 2019; 397 Carrano (10.1016/j.freeradbiomed.2025.08.060_bib23) 2011; 15 Greenberg (10.1016/j.freeradbiomed.2025.08.060_bib18) 2020; 16 Yang (10.1016/j.freeradbiomed.2025.08.060_bib19) 2022; 15 Chu (10.1016/j.freeradbiomed.2025.08.060_bib38) 2011; 69 Gorica (10.1016/j.freeradbiomed.2025.08.060_bib4) 2022; 21 Ivanov (10.1016/j.freeradbiomed.2025.08.060_bib8) 2015; 573 Dandamudi (10.1016/j.freeradbiomed.2025.08.060_bib49) 2023; 24 Orre (10.1016/j.freeradbiomed.2025.08.060_bib46) 2019; 73 Maskrey (10.1016/j.freeradbiomed.2025.08.060_bib56) 2014; 11 Bernstein (10.1016/j.freeradbiomed.2025.08.060_bib17) 2009; 1 Recabarren-Leiva (10.1016/j.freeradbiomed.2025.08.060_bib47) 2021; 166 Calder (10.1016/j.freeradbiomed.2025.08.060_bib3) 2020 Faki (10.1016/j.freeradbiomed.2025.08.060_bib6) 2021; 12 Kulkarni (10.1016/j.freeradbiomed.2025.08.060_bib7) 2000; 22 Choi (10.1016/j.freeradbiomed.2025.08.060_bib37) 2013; 124 Yeung (10.1016/j.freeradbiomed.2025.08.060_bib33) 2011; 9 Rouzer (10.1016/j.freeradbiomed.2025.08.060_bib35) 2020; 120 Rouzer (10.1016/j.freeradbiomed.2025.08.060_bib34) 2009; 50 Yamada (10.1016/j.freeradbiomed.2025.08.060_bib21) 2000; 20 Williams (10.1016/j.freeradbiomed.2025.08.060_bib10) 1999; 18 Chu (10.1016/j.freeradbiomed.2025.08.060_bib30) 2015; 5 Powell (10.1016/j.freeradbiomed.2025.08.060_bib11) 2015; 1851 Bush (10.1016/j.freeradbiomed.2025.08.060_bib36) 1990; 265 Stanger (10.1016/j.freeradbiomed.2025.08.060_bib58) 2023; 246 Turnbull (10.1016/j.freeradbiomed.2025.08.060_bib59) 2022; 158 Shankar Sharma (10.1016/j.freeradbiomed.2025.08.060_bib60) 2023; 142 Epis (10.1016/j.freeradbiomed.2025.08.060_bib24) 2012; 4 Oughtred (10.1016/j.freeradbiomed.2025.08.060_bib43) 2021; 30 Rueden (10.1016/j.freeradbiomed.2025.08.060_bib48) 2017; 18 Cebo (10.1016/j.freeradbiomed.2025.08.060_bib52) 2022; 139 Alonso-López (10.1016/j.freeradbiomed.2025.08.060_bib42) 2019; 2019 Unsworth (10.1016/j.freeradbiomed.2025.08.060_bib51) 2021; 106 Amoah (10.1016/j.freeradbiomed.2025.08.060_bib13) 2024; 25 Ghiso (10.1016/j.freeradbiomed.2025.08.060_bib61) 2010; 61 Mashima (10.1016/j.freeradbiomed.2025.08.060_bib32) 2015; 6 Chandrasekharan (10.1016/j.freeradbiomed.2025.08.060_bib14) 2004; 5 Czapski (10.1016/j.freeradbiomed.2025.08.060_bib15) 2016; 41 Badimon (10.1016/j.freeradbiomed.2025.08.060_bib1) 2021; 117 Colciaghi (10.1016/j.freeradbiomed.2025.08.060_bib26) 2004; 62 Chen (10.1016/j.freeradbiomed.2025.08.060_bib29) 1995; 213 Turini (10.1016/j.freeradbiomed.2025.08.060_bib5) 2002; 53 Larsen (10.1016/j.freeradbiomed.2025.08.060_bib55) 2023; 43 Poorani (10.1016/j.freeradbiomed.2025.08.060_bib57) 2016; 785 Gremmel (10.1016/j.freeradbiomed.2025.08.060_bib31) 2016; 42 Singh (10.1016/j.freeradbiomed.2025.08.060_bib16) 2019; 73 Verbeek (10.1016/j.freeradbiomed.2025.08.060_bib20) 2009; 66 Lagarde (10.1016/j.freeradbiomed.2025.08.060_bib54) 2018; 1863 Qin (10.1016/j.freeradbiomed.2025.08.060_bib39) 2003; 278
References_xml	– volume: 1863 start-page: 651 year: 2018 end-page: 656 ident: bib54 article-title: Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets publication-title: Biochim. Biophys. Acta Mol. Cell Biol. Lipids – volume: 785 start-page: 116 year: 2016 end-page: 132 ident: bib57 article-title: COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance publication-title: Eur. J. Pharmacol. – volume: 12 year: 2021 ident: bib6 article-title: Different chemical structures and physiological/pathological roles of cyclooxygenases publication-title: Rambam Maimonides Med. J. – volume: 69 start-page: 34 year: 2011 end-page: 46 ident: bib38 article-title: 5-lipoxygenase as an endogenous modulator of amyloid beta formation in vivo publication-title: Ann. Neurol. – volume: 1 start-page: 326 year: 2009 end-page: 331 ident: bib17 article-title: Amyloid-beta protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease publication-title: Nat. Chem. – volume: 66 start-page: 245 year: 2009 end-page: 249 ident: bib20 article-title: Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy publication-title: Ann. Neurol. – volume: 22 start-page: 291 year: 2000 end-page: 298 ident: bib7 article-title: Cyclooxygenase isoenzymes and newer therapeutic potential for selective COX-2 inhibitors publication-title: Methods Find. Exp. Clin. Pharmacol. – volume: 53 start-page: 35 year: 2002 end-page: 57 ident: bib5 article-title: Cyclooxygenase-2: a therapeutic target publication-title: Annu. Rev. Med. – volume: 18 start-page: 7908 year: 1999 end-page: 7916 ident: bib10 article-title: The role of cyclooxygenases in inflammation, cancer, and development publication-title: Oncogene – volume: 120 start-page: 7592 year: 2020 end-page: 7641 ident: bib35 article-title: Structural and chemical biology of the interaction of cyclooxygenase with substrates and non-steroidal anti-inflammatory drugs publication-title: Chem. Rev. – volume: 20 start-page: 8 year: 2000 end-page: 22 ident: bib21 article-title: Cerebral amyloid angiopathy: an overview publication-title: Neuropathology – volume: 15 start-page: 1167 year: 2011 end-page: 1178 ident: bib23 article-title: Amyloid beta induces oxidative stress-mediated blood-brain barrier changes in capillary amyloid angiopathy publication-title: Antioxidants Redox Signal. – volume: 5 year: 2015 ident: bib30 article-title: Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence publication-title: Sci. Rep. – volume: 16 start-page: 30 year: 2020 end-page: 42 ident: bib18 article-title: Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways publication-title: Nat. Rev. Neurol. – volume: 44 start-page: D536 year: 2015 end-page: D541 ident: bib41 article-title: Integrated interactions database: tissue-specific view of the human and model organism interactomes publication-title: Nucleic Acids Res. – volume: 6 start-page: 297 year: 2015 end-page: 310 ident: bib32 article-title: The role of lipoxygenases in pathophysiology; new insights and future perspectives publication-title: Redox Biol. – volume: 73 start-page: 28 year: 2019 end-page: 45 ident: bib16 article-title: Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies publication-title: Prog. Lipid Res. – volume: 19 start-page: 699 year: 2012 end-page: 710 ident: bib50 article-title: Rational design of small molecule inhibitors targeting RhoA subfamily rho GTPases publication-title: Chem. Biol. – volume: 43 start-page: 1990 year: 2023 end-page: 2007 ident: bib55 article-title: Loss of 12-Lipoxygenase improves the post-transfusion function of stored platelets publication-title: Arterioscler. Thromb. Vasc. Biol. – volume: 21 start-page: 118 year: 2022 end-page: 129 ident: bib4 article-title: Arachidonic acid derivatives and neuroinflammation publication-title: CNS Neurol. Disord.: Drug Targets – volume: 4 start-page: 193 year: 2002 end-page: 201 ident: bib22 article-title: Amyloid beta-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer's disease brain exists publication-title: J. Alzheimers Dis. – volume: 106 start-page: 1968 year: 2021 end-page: 1978 ident: bib51 article-title: Antiplatelet properties of pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling publication-title: Haematologica – volume: 246 year: 2023 ident: bib58 article-title: Bioactive lipid regulation of platelet function, hemostasis, and thrombosis publication-title: Pharmacol. Ther. – volume: 5 start-page: 241 year: 2004 ident: bib14 article-title: The cyclooxygenases publication-title: Genome Biol. – volume: 38 start-page: 503 year: 2014 end-page: 506 ident: bib25 article-title: Modulation of amyloid-beta production by leukotriene B4 via the gamma-secretase pathway publication-title: J. Alzheimers Dis. – volume: 15 start-page: 800 year: 2018 end-page: 808 ident: bib27 article-title: Platelet tau protein as a potential peripheral biomarker in Alzheimer's disease: an explorative study publication-title: Curr. Alzheimer Res. – volume: 213 start-page: 96 year: 1995 end-page: 103 ident: bib29 article-title: Platelets are the primary source of amyloid beta-peptide in human blood publication-title: Biochem. Biophys. Res. Commun. – volume: 117 start-page: 2001 year: 2021 end-page: 2015 ident: bib1 article-title: The key contribution of platelet and vascular arachidonic acid metabolism to the pathophysiology of atherothrombosis publication-title: Cardiovasc. Res. – volume: 8 year: 2019 ident: bib2 article-title: Arachidonic acid evokes an increase in intracellular Ca(2+) concentration and nitric oxide production in endothelial cells from human brain microcirculation publication-title: Cells – volume: 62 start-page: 498 year: 2004 end-page: 501 ident: bib26 article-title: Platelet APP, ADAM 10 and BACE alterations in the early stages of Alzheimer disease publication-title: Neurology – volume: 61 year: 2010 ident: bib61 article-title: Cerebral amyloid angiopathy and Alzheimer's disease publication-title: Hirosaki igaku Hirosaki Med. J. – volume: 24 year: 2023 ident: bib49 article-title: Structure-activity relationship analysis of rhosin, a RhoA GTPase inhibitor, reveals a new class of antiplatelet agents publication-title: Int. J. Mol. Sci. – start-page: 1 year: 2020 end-page: 13 ident: bib3 article-title: n-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside publication-title: Proc. Nutr. Soc. – volume: 265 start-page: 15977 year: 1990 end-page: 15983 ident: bib36 article-title: The amyloid precursor protein of Alzheimer's disease is released by human platelets publication-title: J. Biol. Chem. – volume: 73 start-page: 166 year: 2019 end-page: 182.e167 ident: bib46 article-title: SubCellBarCode: proteome-wide mapping of protein localization and relocalization publication-title: Mol. Cell – volume: 397 start-page: 159 year: 2019 end-page: 171 ident: bib28 article-title: The cAMP/PKA pathway inhibits beta-amyloid peptide release from human platelets publication-title: Neuroscience – volume: 36 start-page: 2628 year: 2020 end-page: 2629 ident: bib45 article-title: ShinyGO: a graphical gene-set enrichment tool for animals and plants publication-title: Bioinformatics – volume: 11 start-page: 33 year: 2014 ident: bib56 article-title: 12-hydroxyeicosatetraenoic acid is associated with variability in aspirin-induced platelet inhibition publication-title: J. Inflamm. – volume: 142 year: 2023 ident: bib60 article-title: Non-enzymatic role of platelet 12-LOX in platelet activation publication-title: Blood – volume: 278 start-page: 50970 year: 2003 end-page: 50977 ident: bib39 article-title: Cyclooxygenase (COX)-2 and COX-1 potentiate β-amyloid peptide generation through mechanisms that involve γ-secretase activity publication-title: J. Biol. Chem. – volume: 1851 start-page: 340 year: 2015 end-page: 355 ident: bib11 article-title: Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid publication-title: Biochim. Biophys. Acta – volume: 42 start-page: 191 year: 2016 end-page: 204 ident: bib31 article-title: Platelet physiology publication-title: Semin. Thromb. Hemost. – volume: 158 year: 2022 ident: bib59 article-title: Profiling oxylipins released from human platelets activated through the GPVI collagen receptor publication-title: Prostag. Other Lipid Mediat. – volume: 42 start-page: D358 year: 2013 end-page: D363 ident: bib40 article-title: The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases publication-title: Nucleic Acids Res. – volume: 25 year: 2024 ident: bib13 article-title: Lipoxygenases at the intersection of infection and carcinogenesis publication-title: Int. J. Mol. Sci. – volume: 166 start-page: 1149 year: 2021 end-page: 1161 ident: bib47 article-title: Effects of the age/rage axis in the platelet activation publication-title: Int. J. Biol. Macromol. – volume: 2019 year: 2019 ident: bib9 article-title: Emerging roles of 5-Lipoxygenase phosphorylation in inflammation and cell death publication-title: Oxid. Med. Cell. Longev. – volume: 15 year: 2022 ident: bib19 article-title: Based on molecular structures: amyloid-beta generation, clearance, toxicity and therapeutic strategies publication-title: Front. Mol. Neurosci. – volume: 50 year: 2009 ident: bib34 article-title: Cyclooxygenases: structural and functional insights publication-title: J. Lipid Res. – volume: 30 start-page: 187 year: 2021 end-page: 200 ident: bib43 article-title: The BioGRID database: a comprehensive biomedical resource of curated protein, genetic, and chemical interactions publication-title: Protein Sci. – volume: 139 start-page: 1722 year: 2022 end-page: 1742 ident: bib52 article-title: Platelet ACKR3/CXCR7 favors antiplatelet lipids over an atherothrombotic lipidome and regulates thromboinflammation publication-title: Blood – volume: 4 start-page: 1126 year: 2012 end-page: 1150 ident: bib24 article-title: Alpha, beta-and gamma-secretases in Alzheimer's disease publication-title: Front. Biosci. – volume: 15 year: 2024 ident: bib53 article-title: Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention publication-title: Front. Pharmacol. – volume: 2019 year: 2019 ident: bib42 article-title: APID database: redefining protein–protein interaction experimental evidences and binary interactomes publication-title: Database – volume: 573 start-page: 1 year: 2015 end-page: 32 ident: bib8 article-title: Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15) publication-title: Gene – volume: 18 start-page: 529 year: 2017 ident: bib48 article-title: ImageJ2: imagej for the next generation of scientific image data publication-title: BMC Bioinf. – volume: 124 start-page: 59 year: 2013 end-page: 68 ident: bib37 article-title: Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease publication-title: J. Neurochem. – volume: 9 start-page: 154 year: 2011 end-page: 164 ident: bib33 article-title: 12-lipoxygenase: a potential target for novel anti-platelet therapeutics publication-title: Cardiovasc. Hematol. Agents Med. Chem. – volume: 119 start-page: e22 year: 2012 end-page: e34 ident: bib44 article-title: PlateletWeb: a systems biologic analysis of signaling networks in human platelets publication-title: Blood – volume: 13 start-page: 684 year: 2021 end-page: 696 ident: bib12 article-title: Arachidonic acid 15-Lipoxygenase: effects of its expression, metabolites, and genetic and epigenetic variations on airway inflammation publication-title: Allergy Asthma Immunol. Res. – volume: 41 start-page: 243 year: 2016 end-page: 257 ident: bib15 article-title: The lipoxygenases: their regulation and implication in Alzheimer's disease publication-title: Neurochem. Res. – volume: 573 start-page: 1 year: 2015 ident: 10.1016/j.freeradbiomed.2025.08.060_bib8 article-title: Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15) publication-title: Gene doi: 10.1016/j.gene.2015.07.073 – volume: 124 start-page: 59 year: 2013 ident: 10.1016/j.freeradbiomed.2025.08.060_bib37 article-title: Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease publication-title: J. Neurochem. doi: 10.1111/jnc.12059 – volume: 41 start-page: 243 year: 2016 ident: 10.1016/j.freeradbiomed.2025.08.060_bib15 article-title: The lipoxygenases: their regulation and implication in Alzheimer's disease publication-title: Neurochem. Res. doi: 10.1007/s11064-015-1776-x – volume: 1 start-page: 326 year: 2009 ident: 10.1016/j.freeradbiomed.2025.08.060_bib17 article-title: Amyloid-beta protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease publication-title: Nat. Chem. doi: 10.1038/nchem.247 – volume: 117 start-page: 2001 year: 2021 ident: 10.1016/j.freeradbiomed.2025.08.060_bib1 article-title: The key contribution of platelet and vascular arachidonic acid metabolism to the pathophysiology of atherothrombosis publication-title: Cardiovasc. Res. doi: 10.1093/cvr/cvab003 – volume: 19 start-page: 699 year: 2012 ident: 10.1016/j.freeradbiomed.2025.08.060_bib50 article-title: Rational design of small molecule inhibitors targeting RhoA subfamily rho GTPases publication-title: Chem. Biol. doi: 10.1016/j.chembiol.2012.05.009 – start-page: 1 year: 2020 ident: 10.1016/j.freeradbiomed.2025.08.060_bib3 article-title: n-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside publication-title: Proc. Nutr. Soc. – volume: 1851 start-page: 340 year: 2015 ident: 10.1016/j.freeradbiomed.2025.08.060_bib11 article-title: Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbalip.2014.10.008 – volume: 61 year: 2010 ident: 10.1016/j.freeradbiomed.2025.08.060_bib61 article-title: Cerebral amyloid angiopathy and Alzheimer's disease publication-title: Hirosaki igaku Hirosaki Med. J. – volume: 18 start-page: 7908 year: 1999 ident: 10.1016/j.freeradbiomed.2025.08.060_bib10 article-title: The role of cyclooxygenases in inflammation, cancer, and development publication-title: Oncogene doi: 10.1038/sj.onc.1203286 – volume: 25 year: 2024 ident: 10.1016/j.freeradbiomed.2025.08.060_bib13 article-title: Lipoxygenases at the intersection of infection and carcinogenesis publication-title: Int. J. Mol. Sci. doi: 10.3390/ijms25073961 – volume: 15 start-page: 800 year: 2018 ident: 10.1016/j.freeradbiomed.2025.08.060_bib27 article-title: Platelet tau protein as a potential peripheral biomarker in Alzheimer's disease: an explorative study publication-title: Curr. Alzheimer Res. doi: 10.2174/1567205015666180404165915 – volume: 30 start-page: 187 year: 2021 ident: 10.1016/j.freeradbiomed.2025.08.060_bib43 article-title: The BioGRID database: a comprehensive biomedical resource of curated protein, genetic, and chemical interactions publication-title: Protein Sci. doi: 10.1002/pro.3978 – volume: 1863 start-page: 651 year: 2018 ident: 10.1016/j.freeradbiomed.2025.08.060_bib54 article-title: Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets publication-title: Biochim. Biophys. Acta Mol. Cell Biol. Lipids doi: 10.1016/j.bbalip.2018.03.005 – volume: 22 start-page: 291 year: 2000 ident: 10.1016/j.freeradbiomed.2025.08.060_bib7 article-title: Cyclooxygenase isoenzymes and newer therapeutic potential for selective COX-2 inhibitors publication-title: Methods Find. Exp. Clin. Pharmacol. doi: 10.1358/mf.2000.22.5.796648 – volume: 12 year: 2021 ident: 10.1016/j.freeradbiomed.2025.08.060_bib6 article-title: Different chemical structures and physiological/pathological roles of cyclooxygenases publication-title: Rambam Maimonides Med. J. doi: 10.5041/RMMJ.10426 – volume: 11 start-page: 33 year: 2014 ident: 10.1016/j.freeradbiomed.2025.08.060_bib56 article-title: 12-hydroxyeicosatetraenoic acid is associated with variability in aspirin-induced platelet inhibition publication-title: J. Inflamm. doi: 10.1186/s12950-014-0033-4 – volume: 119 start-page: e22 year: 2012 ident: 10.1016/j.freeradbiomed.2025.08.060_bib44 article-title: PlateletWeb: a systems biologic analysis of signaling networks in human platelets publication-title: Blood doi: 10.1182/blood-2011-10-387308 – volume: 42 start-page: D358 year: 2013 ident: 10.1016/j.freeradbiomed.2025.08.060_bib40 article-title: The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkt1115 – volume: 50 year: 2009 ident: 10.1016/j.freeradbiomed.2025.08.060_bib34 article-title: Cyclooxygenases: structural and functional insights publication-title: J. Lipid Res. doi: 10.1194/jlr.R800042-JLR200 – volume: 15 year: 2024 ident: 10.1016/j.freeradbiomed.2025.08.060_bib53 article-title: Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention publication-title: Front. Pharmacol. doi: 10.3389/fphar.2024.1520488 – volume: 265 start-page: 15977 year: 1990 ident: 10.1016/j.freeradbiomed.2025.08.060_bib36 article-title: The amyloid precursor protein of Alzheimer's disease is released by human platelets publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)55493-4 – volume: 16 start-page: 30 year: 2020 ident: 10.1016/j.freeradbiomed.2025.08.060_bib18 article-title: Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways publication-title: Nat. Rev. Neurol. doi: 10.1038/s41582-019-0281-2 – volume: 53 start-page: 35 year: 2002 ident: 10.1016/j.freeradbiomed.2025.08.060_bib5 article-title: Cyclooxygenase-2: a therapeutic target publication-title: Annu. Rev. Med. doi: 10.1146/annurev.med.53.082901.103952 – volume: 43 start-page: 1990 year: 2023 ident: 10.1016/j.freeradbiomed.2025.08.060_bib55 article-title: Loss of 12-Lipoxygenase improves the post-transfusion function of stored platelets publication-title: Arterioscler. Thromb. Vasc. Biol. doi: 10.1161/ATVBAHA.123.319021 – volume: 24 year: 2023 ident: 10.1016/j.freeradbiomed.2025.08.060_bib49 article-title: Structure-activity relationship analysis of rhosin, a RhoA GTPase inhibitor, reveals a new class of antiplatelet agents publication-title: Int. J. Mol. Sci. doi: 10.3390/ijms24044167 – volume: 5 year: 2015 ident: 10.1016/j.freeradbiomed.2025.08.060_bib30 article-title: Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence publication-title: Sci. Rep. doi: 10.1038/srep11086 – volume: 4 start-page: 193 year: 2002 ident: 10.1016/j.freeradbiomed.2025.08.060_bib22 article-title: Amyloid beta-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer's disease brain exists publication-title: J. Alzheimers Dis. doi: 10.3233/JAD-2002-4309 – volume: 8 year: 2019 ident: 10.1016/j.freeradbiomed.2025.08.060_bib2 article-title: Arachidonic acid evokes an increase in intracellular Ca(2+) concentration and nitric oxide production in endothelial cells from human brain microcirculation publication-title: Cells doi: 10.3390/cells8070689 – volume: 2019 year: 2019 ident: 10.1016/j.freeradbiomed.2025.08.060_bib9 article-title: Emerging roles of 5-Lipoxygenase phosphorylation in inflammation and cell death publication-title: Oxid. Med. Cell. Longev. doi: 10.1155/2019/2749173 – volume: 21 start-page: 118 year: 2022 ident: 10.1016/j.freeradbiomed.2025.08.060_bib4 article-title: Arachidonic acid derivatives and neuroinflammation publication-title: CNS Neurol. Disord.: Drug Targets doi: 10.2174/1871527320666210208130412 – volume: 106 start-page: 1968 year: 2021 ident: 10.1016/j.freeradbiomed.2025.08.060_bib51 article-title: Antiplatelet properties of pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling publication-title: Haematologica doi: 10.3324/haematol.2019.223529 – volume: 4 start-page: 1126 year: 2012 ident: 10.1016/j.freeradbiomed.2025.08.060_bib24 article-title: Alpha, beta-and gamma-secretases in Alzheimer's disease publication-title: Front. Biosci. – volume: 158 year: 2022 ident: 10.1016/j.freeradbiomed.2025.08.060_bib59 article-title: Profiling oxylipins released from human platelets activated through the GPVI collagen receptor publication-title: Prostag. Other Lipid Mediat. doi: 10.1016/j.prostaglandins.2021.106607 – volume: 278 start-page: 50970 year: 2003 ident: 10.1016/j.freeradbiomed.2025.08.060_bib39 article-title: Cyclooxygenase (COX)-2 and COX-1 potentiate β-amyloid peptide generation through mechanisms that involve γ-secretase activity publication-title: J. Biol. Chem. doi: 10.1074/jbc.M307699200 – volume: 44 start-page: D536 year: 2015 ident: 10.1016/j.freeradbiomed.2025.08.060_bib41 article-title: Integrated interactions database: tissue-specific view of the human and model organism interactomes publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkv1115 – volume: 73 start-page: 28 year: 2019 ident: 10.1016/j.freeradbiomed.2025.08.060_bib16 article-title: Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies publication-title: Prog. Lipid Res. doi: 10.1016/j.plipres.2018.11.001 – volume: 120 start-page: 7592 year: 2020 ident: 10.1016/j.freeradbiomed.2025.08.060_bib35 article-title: Structural and chemical biology of the interaction of cyclooxygenase with substrates and non-steroidal anti-inflammatory drugs publication-title: Chem. Rev. doi: 10.1021/acs.chemrev.0c00215 – volume: 166 start-page: 1149 year: 2021 ident: 10.1016/j.freeradbiomed.2025.08.060_bib47 article-title: Effects of the age/rage axis in the platelet activation publication-title: Int. J. Biol. Macromol. doi: 10.1016/j.ijbiomac.2020.10.270 – volume: 139 start-page: 1722 year: 2022 ident: 10.1016/j.freeradbiomed.2025.08.060_bib52 article-title: Platelet ACKR3/CXCR7 favors antiplatelet lipids over an atherothrombotic lipidome and regulates thromboinflammation publication-title: Blood doi: 10.1182/blood.2021013097 – volume: 20 start-page: 8 year: 2000 ident: 10.1016/j.freeradbiomed.2025.08.060_bib21 article-title: Cerebral amyloid angiopathy: an overview publication-title: Neuropathology doi: 10.1046/j.1440-1789.2000.00268.x – volume: 42 start-page: 191 year: 2016 ident: 10.1016/j.freeradbiomed.2025.08.060_bib31 article-title: Platelet physiology publication-title: Semin. Thromb. Hemost. doi: 10.1055/s-0035-1564835 – volume: 38 start-page: 503 year: 2014 ident: 10.1016/j.freeradbiomed.2025.08.060_bib25 article-title: Modulation of amyloid-beta production by leukotriene B4 via the gamma-secretase pathway publication-title: J. Alzheimers Dis. doi: 10.3233/JAD-131223 – volume: 15 year: 2022 ident: 10.1016/j.freeradbiomed.2025.08.060_bib19 article-title: Based on molecular structures: amyloid-beta generation, clearance, toxicity and therapeutic strategies publication-title: Front. Mol. Neurosci. doi: 10.3389/fnmol.2022.927530 – volume: 69 start-page: 34 year: 2011 ident: 10.1016/j.freeradbiomed.2025.08.060_bib38 article-title: 5-lipoxygenase as an endogenous modulator of amyloid beta formation in vivo publication-title: Ann. Neurol. doi: 10.1002/ana.22234 – volume: 18 start-page: 529 year: 2017 ident: 10.1016/j.freeradbiomed.2025.08.060_bib48 article-title: ImageJ2: imagej for the next generation of scientific image data publication-title: BMC Bioinf. doi: 10.1186/s12859-017-1934-z – volume: 785 start-page: 116 year: 2016 ident: 10.1016/j.freeradbiomed.2025.08.060_bib57 article-title: COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance publication-title: Eur. J. Pharmacol. doi: 10.1016/j.ejphar.2015.08.049 – volume: 5 start-page: 241 year: 2004 ident: 10.1016/j.freeradbiomed.2025.08.060_bib14 article-title: The cyclooxygenases publication-title: Genome Biol. doi: 10.1186/gb-2004-5-9-241 – volume: 9 start-page: 154 year: 2011 ident: 10.1016/j.freeradbiomed.2025.08.060_bib33 article-title: 12-lipoxygenase: a potential target for novel anti-platelet therapeutics publication-title: Cardiovasc. Hematol. Agents Med. Chem. doi: 10.2174/187152511797037619 – volume: 66 start-page: 245 year: 2009 ident: 10.1016/j.freeradbiomed.2025.08.060_bib20 article-title: Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy publication-title: Ann. Neurol. doi: 10.1002/ana.21694 – volume: 142 year: 2023 ident: 10.1016/j.freeradbiomed.2025.08.060_bib60 article-title: Non-enzymatic role of platelet 12-LOX in platelet activation publication-title: Blood – volume: 246 year: 2023 ident: 10.1016/j.freeradbiomed.2025.08.060_bib58 article-title: Bioactive lipid regulation of platelet function, hemostasis, and thrombosis publication-title: Pharmacol. Ther. doi: 10.1016/j.pharmthera.2023.108420 – volume: 62 start-page: 498 year: 2004 ident: 10.1016/j.freeradbiomed.2025.08.060_bib26 article-title: Platelet APP, ADAM 10 and BACE alterations in the early stages of Alzheimer disease publication-title: Neurology doi: 10.1212/01.WNL.0000106953.49802.9C – volume: 397 start-page: 159 year: 2019 ident: 10.1016/j.freeradbiomed.2025.08.060_bib28 article-title: The cAMP/PKA pathway inhibits beta-amyloid peptide release from human platelets publication-title: Neuroscience doi: 10.1016/j.neuroscience.2018.11.025 – volume: 2019 year: 2019 ident: 10.1016/j.freeradbiomed.2025.08.060_bib42 article-title: APID database: redefining protein–protein interaction experimental evidences and binary interactomes publication-title: Database doi: 10.1093/database/baz005 – volume: 36 start-page: 2628 year: 2020 ident: 10.1016/j.freeradbiomed.2025.08.060_bib45 article-title: ShinyGO: a graphical gene-set enrichment tool for animals and plants publication-title: Bioinformatics doi: 10.1093/bioinformatics/btz931 – volume: 213 start-page: 96 year: 1995 ident: 10.1016/j.freeradbiomed.2025.08.060_bib29 article-title: Platelets are the primary source of amyloid beta-peptide in human blood publication-title: Biochem. Biophys. Res. Commun. doi: 10.1006/bbrc.1995.2103 – volume: 73 start-page: 166 year: 2019 ident: 10.1016/j.freeradbiomed.2025.08.060_bib46 article-title: SubCellBarCode: proteome-wide mapping of protein localization and relocalization publication-title: Mol. Cell doi: 10.1016/j.molcel.2018.11.035 – volume: 15 start-page: 1167 year: 2011 ident: 10.1016/j.freeradbiomed.2025.08.060_bib23 article-title: Amyloid beta induces oxidative stress-mediated blood-brain barrier changes in capillary amyloid angiopathy publication-title: Antioxidants Redox Signal. doi: 10.1089/ars.2011.3895 – volume: 6 start-page: 297 year: 2015 ident: 10.1016/j.freeradbiomed.2025.08.060_bib32 article-title: The role of lipoxygenases in pathophysiology; new insights and future perspectives publication-title: Redox Biol. doi: 10.1016/j.redox.2015.08.006 – volume: 13 start-page: 684 year: 2021 ident: 10.1016/j.freeradbiomed.2025.08.060_bib12 article-title: Arachidonic acid 15-Lipoxygenase: effects of its expression, metabolites, and genetic and epigenetic variations on airway inflammation publication-title: Allergy Asthma Immunol. Res. doi: 10.4168/aair.2021.13.5.684
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Snippet	Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal...
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SubjectTerms	Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer Disease - pathology Amyloid beta-Peptides - genetics Amyloid beta-Peptides - metabolism Amyloid-β Arachidonate 12-Lipoxygenase - genetics Arachidonate 12-Lipoxygenase - metabolism Blood Platelets - enzymology Blood Platelets - metabolism Cerebral Amyloid Angiopathy - genetics Cerebral Amyloid Angiopathy - metabolism Cerebral Amyloid Angiopathy - pathology Cyclooxygenase Cyclooxygenase 1 - genetics Cyclooxygenase 1 - metabolism Humans Lipoxygenase Peptide Fragments - metabolism Platelet Activation Platelets rhoA GTP-Binding Protein - genetics rhoA GTP-Binding Protein - metabolism Signal Transduction
Title	Platelet COX and LOX enzymes orchestrate amyloid-β secretion via RhoA signaling: Implications for neurodegenerative diseases
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