Mice lacking alpha-synuclein are resistant to mitochondrial toxins

Mice lacking alpha-synuclein are resistant to mitochondrial toxins

Abnormalities in the function of α-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that α-synuclein-deficient mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There was dose-dependent protection against loss of both dopamine in the stri...

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Main Authors: Peter Klivenyi, Donald Siwek, Gabrielle Gardian, Lichuan Yang, Anatoly Starkov, Carine Cleren, Robert J. Ferrante, Neil W. Kowall, Asa Abeliovich, M. Flint Beal
Format: Article
Language:English
Published: Elsevier 2006-03-01
Series:Neurobiology of Disease
Subjects:
MPTP
Paraquat
3-Nitropropionic acid
Malonate
MPP+
MPP+ levels
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996105002421
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spelling doaj-614396f73bb445cbb6513e67f25816df2021-03-20T04:52:00ZengElsevierNeurobiology of Disease1095-953X2006-03-01213541548Mice lacking alpha-synuclein are resistant to mitochondrial toxinsPeter Klivenyi0Donald Siwek1Gabrielle Gardian2Lichuan Yang3Anatoly Starkov4Carine Cleren5Robert J. Ferrante6Neil W. Kowall7Asa Abeliovich8M. Flint Beal9Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USAGeriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, MA and Neurology, Pathology, and Psychiatry Departments, Boston University School of Medicine, Boston, MA 02118, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USAGeriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, MA and Neurology, Pathology, and Psychiatry Departments, Boston University School of Medicine, Boston, MA 02118, USAGeriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, MA and Neurology, Pathology, and Psychiatry Departments, Boston University School of Medicine, Boston, MA 02118, USADepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York -Presbyterian Hospital, New York, NY 10021, USADepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USA; Corresponding author. Fax: +1 212 746 8532.Abnormalities in the function of α-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that α-synuclein-deficient mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There was dose-dependent protection against loss of both dopamine in the striatum and dopamine transporter (DAT) immunoreactive neurons in the substantia nigra. These effects were not due to alterations in MPTP processing. We found that α-synuclein-deficient mice are also resistant to both malonate and 3-nitropropionic acid (3-NP) neurotoxicity. There was reduced generation of reactive oxygen species in α-synuclein-deficient mice following administration of 3-NP. These findings implicate α-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins.http://www.sciencedirect.com/science/article/pii/S0969996105002421MPTPParaquat3-Nitropropionic acidMalonateMPP+MPP+ levels
collection DOAJ
language English
format Article
sources DOAJ
author Peter Klivenyi
Donald Siwek
Gabrielle Gardian
Lichuan Yang
Anatoly Starkov
Carine Cleren
Robert J. Ferrante
Neil W. Kowall
Asa Abeliovich
M. Flint Beal
spellingShingle Peter Klivenyi
Donald Siwek
Gabrielle Gardian
Lichuan Yang
Anatoly Starkov
Carine Cleren
Robert J. Ferrante
Neil W. Kowall
Asa Abeliovich
M. Flint Beal
Mice lacking alpha-synuclein are resistant to mitochondrial toxins
Neurobiology of Disease
MPTP
Paraquat
3-Nitropropionic acid
Malonate
MPP+
MPP+ levels
author_facet Peter Klivenyi
Donald Siwek
Gabrielle Gardian
Lichuan Yang
Anatoly Starkov
Carine Cleren
Robert J. Ferrante
Neil W. Kowall
Asa Abeliovich
M. Flint Beal
author_sort Peter Klivenyi
title Mice lacking alpha-synuclein are resistant to mitochondrial toxins
title_short Mice lacking alpha-synuclein are resistant to mitochondrial toxins
title_full Mice lacking alpha-synuclein are resistant to mitochondrial toxins
title_fullStr Mice lacking alpha-synuclein are resistant to mitochondrial toxins
title_full_unstemmed Mice lacking alpha-synuclein are resistant to mitochondrial toxins
title_sort mice lacking alpha-synuclein are resistant to mitochondrial toxins
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2006-03-01
description Abnormalities in the function of α-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that α-synuclein-deficient mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There was dose-dependent protection against loss of both dopamine in the striatum and dopamine transporter (DAT) immunoreactive neurons in the substantia nigra. These effects were not due to alterations in MPTP processing. We found that α-synuclein-deficient mice are also resistant to both malonate and 3-nitropropionic acid (3-NP) neurotoxicity. There was reduced generation of reactive oxygen species in α-synuclein-deficient mice following administration of 3-NP. These findings implicate α-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins.
topic MPTP
Paraquat
3-Nitropropionic acid
Malonate
MPP+
MPP+ levels
url http://www.sciencedirect.com/science/article/pii/S0969996105002421
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