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Start Over Author "Itoyama, Yasuto" Journal journal of neurochemistry
5 results on '"Itoyama, Yasuto"'

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

Author

Furukawa K, Matsuzaki-Kobayashi M, Hasegawa T, Kikuchi A, Sugeno N, Itoyama Y, Wang Y, Yao PJ, Bushlin I, and Takeda A

Subjects
Calcium metabolism, Calcium Channel Blockers pharmacology, Calcium Channels drug effects, Calcium Signaling drug effects, Calcium Signaling genetics, Cell Death drug effects, Cell Death genetics, Cell Line, Tumor, Cell Membrane drug effects, Cell Membrane genetics, Cell Membrane Permeability drug effects, Chelating Agents pharmacology, Dopamine metabolism, Humans, Mutation genetics, Nerve Degeneration genetics, Neurons drug effects, Parkinson Disease genetics, Parkinson Disease metabolism, Parkinson Disease physiopathology, alpha-Synuclein genetics, Calcium Channels metabolism, Cell Membrane metabolism, Cell Membrane Permeability genetics, Nerve Degeneration metabolism, Neurons metabolism, alpha-Synuclein metabolism
Abstract

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 neither L-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.

Published
2006
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