The P66ShcMitochondrial Permeability Transition Pore Pathway Determines Neurodegeneration
Joint Authors
Giorgio, Marco
Pelicci, PierGiuseppe
Savino, Costanza
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-05-15
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Mitochondrial-mediated oxidative stress and apoptosis play a crucial role in neurodegenerative disease and aging.
Both mitochondrial permeability transition (PT) and swelling of mitochondria have been involved in neurodegeneration.
Indeed, knockout mice for cyclophilin-D (Cyc-D), a key regulatory component of the PT pore (PTP) that triggers mitochondrial swelling, resulted to be protected in preclinical models of multiple sclerosis (MS), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).
However, how neuronal stress is transduced into mitochondrial oxidative stress and swelling is unclear.
Recently, the aging determinant p66Shc that generates H2O2 reacting with cytochrome c and induces oxidation of PTP and mitochondrial swelling was found to be involved in MS and ALS.
To investigate the role of p66Shc/PTP pathway in neurodegeneration, we performed experimental autoimmune encephalomyelitis (EAE) experiments in p66Shc knockout mice (p66Shc−/−), knock out mice for cyclophilin-D (Cyc-D−/−), and p66Shc Cyc-D double knock out (p66Shc/Cyc-D−/−) mice.
Results confirm that deletion of p66Shc protects from EAE without affecting immune response, whereas it is not epistatic to the Cyc-D mutation.
These findings demonstrate that p66Shc contributes to EAE induced neuronal damage most likely through the opening of PTP suggesting that p66Shc/PTP pathway transduces neurodegenerative stresses.
American Psychological Association (APA)
Savino, Costanza& Pelicci, PierGiuseppe& Giorgio, Marco. 2013. The P66ShcMitochondrial Permeability Transition Pore Pathway Determines Neurodegeneration. Oxidative Medicine and Cellular Longevity،Vol. 2013, no. 2013, pp.1-7.
https://search.emarefa.net/detail/BIM-493164
Modern Language Association (MLA)
Savino, Costanza…[et al.]. The P66ShcMitochondrial Permeability Transition Pore Pathway Determines Neurodegeneration. Oxidative Medicine and Cellular Longevity No. 2013 (2013), pp.1-7.
https://search.emarefa.net/detail/BIM-493164
American Medical Association (AMA)
Savino, Costanza& Pelicci, PierGiuseppe& Giorgio, Marco. The P66ShcMitochondrial Permeability Transition Pore Pathway Determines Neurodegeneration. Oxidative Medicine and Cellular Longevity. 2013. Vol. 2013, no. 2013, pp.1-7.
https://search.emarefa.net/detail/BIM-493164
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-493164