Endoplasmic reticulum dysfunction in neurological disease

Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin...

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Vydané v:Lancet neurology Ročník 12; číslo 1; s. 105 - 118
Hlavní autori: Roussel, Benoit D, Kruppa, Antonina J, Miranda, Elena, Crowther, Damian C, Lomas, David A, Marciniak, Stefan J
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Elsevier Ltd 01.01.2013
Elsevier Limited
Elsevier
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ISSN:1474-4422, 1474-4465, 1474-4465
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Abstract Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid β induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.
AbstractList Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid β induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.
Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid β induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid β induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.
Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid [beta] induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.
Summary Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid β induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.
Endoplasmic reticulum (ER) dysfunction is important in the pathogenesis of many neurological diseases. In this review, we examine the evidence for ER dysfunction in a range of neurological conditions including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). Protein misfolding in the endoplasmic reticulum initiates a well-studied 'Unfolded Protein Response' in energy-starved neurones during stroke that is relevant to the toxicity of reperfusion. The toxic peptide Aβ induces 'ER stress' in Alzheimer's disease leading to activation of similar pathways, while the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood 'ER overload response'. In other neurological disorders such as Parkinson's and Huntington's diseases ER dysfunction is well recognised but the mechanisms for this are less clear. By targeting components of these signalling responses, it may prove possible to ameliorate their toxic effects and treat a range of neurodegenerative conditions.
Author Crowther, Damian C
Lomas, David A
Miranda, Elena
Roussel, Benoit D
Kruppa, Antonina J
Marciniak, Stefan J
Author_xml – sequence: 1
  givenname: Benoit D
  surname: Roussel
  fullname: Roussel, Benoit D
  organization: Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
– sequence: 2
  givenname: Antonina J
  surname: Kruppa
  fullname: Kruppa, Antonina J
  organization: Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
– sequence: 3
  givenname: Elena
  surname: Miranda
  fullname: Miranda, Elena
  organization: Charles Darwin Department of Biology and Biotechnology and Institut Pasteur–Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy
– sequence: 4
  givenname: Damian C
  surname: Crowther
  fullname: Crowther, Damian C
  organization: Department of Genetics, University of Cambridge, Cambridge, UK
– sequence: 5
  givenname: David A
  surname: Lomas
  fullname: Lomas, David A
  organization: Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
– sequence: 6
  givenname: Stefan J
  surname: Marciniak
  fullname: Marciniak, Stefan J
  email: sjm20@cam.ac.uk
  organization: Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23237905$$D View this record in MEDLINE/PubMed
https://inserm.hal.science/inserm-01296824$$DView record in HAL
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Snippet Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea,...
Summary Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep...
Endoplasmic reticulum (ER) dysfunction is important in the pathogenesis of many neurological diseases. In this review, we examine the evidence for ER...
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StartPage 105
SubjectTerms Alzheimer's disease
Amyloid beta-Peptides
Amyloid beta-Peptides - genetics
Amyotrophic lateral sclerosis
Animals
Ataxia
beta -Amyloid
Cellular Biology
Cognitive ability
Disease
Endoplasmic Reticulum
Endoplasmic Reticulum - pathology
Endoplasmic Reticulum - physiology
Enzymes
Epilepsy
Humans
Inclusion bodies
Ischemia
Life Sciences
Movement disorders
Multiple sclerosis
Mutation
Nervous System Diseases
Nervous System Diseases - genetics
Nervous System Diseases - pathology
Nervous System Diseases - physiopathology
Neurodegenerative diseases
Neurological diseases
Neurology
neuroserpin
Prion protein
Protein Folding
Reperfusion
Signal Transduction
Signal Transduction - physiology
Sleep
Sleep disorders
Stress
Stroke
Unfolded Protein Response
Unfolded Protein Response - genetics
Title Endoplasmic reticulum dysfunction in neurological disease
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https://dx.doi.org/10.1016/S1474-4422(12)70238-7
https://www.ncbi.nlm.nih.gov/pubmed/23237905
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Volume 12
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