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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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Published in: | Journal of neurochemistry 2006-05, Vol.97 (4), p.1071 |
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container_title | Journal of neurochemistry |
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creator | Furukawa, Katsutoshi Matsuzaki-Kobayashi, Michiko Hasegawa, Takafumi Kikuchi, Akio Sugeno, Naoto Itoyama, Yasuto Wang, Yue Yao, Pamela J Bushlin, Ittai Takeda, Atsushi |
description | 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] |
doi_str_mv | 10.1111/j.1471-4159.2006.03803.x |
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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. 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subjects | Ions Membranes Mutation Neurons Parkinson's disease Permeability Plasma |
title | Plasma membrane ion permeability induced by mutant [alpha]-synuclein contributes to the degeneration of neural cells |
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