p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer’s disease

In Alzheimer’s disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerat...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Molecular psychiatry Ročník 20; číslo 11; s. 1301 - 1310
Hlavní autoři:	Yao, X-Q, Jiao, S-S, Saadipour, K, Zeng, F, Wang, Q-H, Zhu, C, Shen, L-L, Zeng, G-H, Liang, C-R, Wang, J, Liu, Y-H, Hou, H-Y, Xu, X, Su, Y-P, Fan, X-T, Xiao, H-L, Lue, L-F, Zeng, Y-Q, Giunta, B, Zhong, J-H, Walker, D G, Zhou, H-D, Tan, J, Zhou, X-F, Wang, Y-J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.11.2015 Nature Publishing Group
Témata:	13/1 13/2 14/19 42/44 631/378 82/29 82/51 82/80 ADAM Proteins - metabolism ADAM17 Protein Age Factors Alzheimer Disease - complications Alzheimer Disease - drug therapy Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism Amyloid beta-Peptides - toxicity Amyloid beta-protein Amyloid beta-Protein Precursor - genetics Animals Apoptosis Apoptosis - physiology Behavioral Sciences Biological Psychology Brain - drug effects Brain - metabolism Brain - pathology Brain research Case-Control Studies Cognition Disorders - etiology Cognition Disorders - therapy Disease Models, Animal Down-Regulation - genetics Enzymes Genetic aspects Hospitals Humans Maze Learning - drug effects Maze Learning - physiology Medical research Medicine Medicine & Public Health Mice Mice, Transgenic Mutation - genetics Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - deficiency Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurodegeneration Neurosciences Neurotrophic functions Original original-article Pharmacotherapy Phosphorylation Physiological aspects Physiology Presenilin-1 - genetics Preventive medicine Protein Structure, Tertiary - physiology Psychiatry Receptors, Nerve Growth Factor - chemistry Receptors, Nerve Growth Factor - deficiency Receptors, Nerve Growth Factor - genetics Recombinant Proteins - therapeutic use Research centers Risk factors Toxicity Transduction, Genetic Tumor necrosis factor-TNF Variance analysis Australia China United States > US
ISSN:	1359-4184, 1476-5578, 1476-5578
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	In Alzheimer’s disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer’s patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equal to this work.
ISSN:	1359-4184 1476-5578 1476-5578
DOI:	10.1038/mp.2015.49