Plasma membrane ion permeability induced by mutant [alpha]-synuclein contributes to the degeneration of neural cells

Mutations in alpha-synuclein cause some cases of familial Parkinson's disease (PD), but the mechanism by which alpha-synuclein promotes degeneration of dopamine-producing neurons is unknown. We report that human neural cells expressing mutant alpha-synuclein (A30P and A53T) have higher plasma m...

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Bibliographic Details
Published in:Journal of neurochemistry 2006-05, Vol.97 (4), p.1071
Main Authors: Furukawa, Katsutoshi, Matsuzaki-Kobayashi, Michiko, Hasegawa, Takafumi, Kikuchi, Akio, Sugeno, Naoto, Itoyama, Yasuto, Wang, Yue, Yao, Pamela J, Bushlin, Ittai, Takeda, Atsushi
Format: Article
Language:English
Subjects:
Ions
Membranes
Mutation
Neurons
Parkinson's disease
Permeability
Plasma
Online Access:Get full text
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Summary:Mutations in alpha-synuclein cause some cases of familial Parkinson's disease (PD), but the mechanism by which alpha-synuclein promotes degeneration of dopamine-producing neurons is unknown. We report that human neural cells expressing mutant alpha-synuclein (A30P and A53T) have higher plasma membrane ion permeability. The higher ion permeability caused by mutant alpha-synuclein would be because of relatively large pores through which most cations can pass non-selectively. Both the basal level of [Ca2+]i and the Ca2+ response to membrane depolarization are greater in cells expressing mutant alpha-synuclein. The membrane permeable Ca2+ chelator BAPTA-AM significantly protected the cells against oxidative stress, whereas neitherl-type (nifedipine) nor N-type (omega-conotoxin-GVIA) Ca2+ channel blockers protected the cells. These findings suggest that the high membrane ion permeability caused by mutant alpha-synuclein may contribute to the degeneration of neurons in PD.[PUBLICATION ABSTRACT]
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2006.03803.x