Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.

Parkinson's disease (PD) is the second most common neurodegenerative disease. A key pathological feature of PD is Lewy bodies, of which the major protein component is α-synuclein (α-syn). Human genetic studies have shown that mutations (A53T, A30P, E46K) and multiplication of the α-syn gene are...

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Autores principales: Li Li, Sashi Nadanaciva, Zdenek Berger, Wei Shen, Katrina Paumier, Joel Schwartz, Kewa Mou, Paula Loos, Anthony J Milici, John Dunlop, Warren D Hirst
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/d66a11a109554bf685a5e666188f4884
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spelling oai:doaj.org-article:d66a11a109554bf685a5e666188f48842021-11-18T08:39:12ZHuman A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.1932-620310.1371/journal.pone.0085815https://doaj.org/article/d66a11a109554bf685a5e666188f48842013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24392030/?tool=EBIhttps://doaj.org/toc/1932-6203Parkinson's disease (PD) is the second most common neurodegenerative disease. A key pathological feature of PD is Lewy bodies, of which the major protein component is α-synuclein (α-syn). Human genetic studies have shown that mutations (A53T, A30P, E46K) and multiplication of the α-syn gene are linked to familial PD. Mice overexpressing the human A53T mutant α-syn gene develop severe movement disorders. However, the molecular mechanisms of α-syn toxicity are not well understood. Recently, mitochondrial dysfunction has been linked with multiple neurodegenerative diseases including Parkinson's disease. Here we investigated whether mitochondrial motility, dynamics and respiratory function are affected in primary neurons from a mouse model expressing the human A53T mutation. We found that mitochondrial motility was selectively inhibited in A53T neurons while transport of other organelles was not affected. In addition, A53T expressing neurons showed impairment in mitochondrial membrane potential and mitochondrial respiratory function. Furthermore, we found that rapamycin, an autophagy inducer, rescued the decreased mitochondrial mobility. Taken together, these data demonstrate that A53T α-syn impairs mitochondrial function and dynamics and the deficit of mitochondrial transport is reversible, providing further understanding of the disease pathogenesis and a potential therapeutic strategy for PD.Li LiSashi NadanacivaZdenek BergerWei ShenKatrina PaumierJoel SchwartzKewa MouPaula LoosAnthony J MiliciJohn DunlopWarren D HirstPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e85815 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Li Li
Sashi Nadanaciva
Zdenek Berger
Wei Shen
Katrina Paumier
Joel Schwartz
Kewa Mou
Paula Loos
Anthony J Milici
John Dunlop
Warren D Hirst
Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
description Parkinson's disease (PD) is the second most common neurodegenerative disease. A key pathological feature of PD is Lewy bodies, of which the major protein component is α-synuclein (α-syn). Human genetic studies have shown that mutations (A53T, A30P, E46K) and multiplication of the α-syn gene are linked to familial PD. Mice overexpressing the human A53T mutant α-syn gene develop severe movement disorders. However, the molecular mechanisms of α-syn toxicity are not well understood. Recently, mitochondrial dysfunction has been linked with multiple neurodegenerative diseases including Parkinson's disease. Here we investigated whether mitochondrial motility, dynamics and respiratory function are affected in primary neurons from a mouse model expressing the human A53T mutation. We found that mitochondrial motility was selectively inhibited in A53T neurons while transport of other organelles was not affected. In addition, A53T expressing neurons showed impairment in mitochondrial membrane potential and mitochondrial respiratory function. Furthermore, we found that rapamycin, an autophagy inducer, rescued the decreased mitochondrial mobility. Taken together, these data demonstrate that A53T α-syn impairs mitochondrial function and dynamics and the deficit of mitochondrial transport is reversible, providing further understanding of the disease pathogenesis and a potential therapeutic strategy for PD.
format article
author Li Li
Sashi Nadanaciva
Zdenek Berger
Wei Shen
Katrina Paumier
Joel Schwartz
Kewa Mou
Paula Loos
Anthony J Milici
John Dunlop
Warren D Hirst
author_facet Li Li
Sashi Nadanaciva
Zdenek Berger
Wei Shen
Katrina Paumier
Joel Schwartz
Kewa Mou
Paula Loos
Anthony J Milici
John Dunlop
Warren D Hirst
author_sort Li Li
title Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
title_short Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
title_full Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
title_fullStr Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
title_full_unstemmed Human A53T α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
title_sort human a53t α-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/d66a11a109554bf685a5e666188f4884
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