Progress research in α-synucleinopathy

Takashi Nonaka, Masami Masuda, Masato Hasegawa

Department of Molecular Neurobiology, Tokyo Institute of Psychiatry

Filamentous inclusions made of alpha-synuclein in neurons and glial cells are the defining neuropathological features of the so-called α-synucleinopathies which include Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy.　Although alpha-synuclein is an abundant presynaptic protein which is deposited in neurons in syncleinopathy brains, the functions of this protein remain to be fully elucidated.　Intracellular deposition of alpha-synuclein is thought to be toxic to cells, but the precise mechanisms how alpha-synuclein is assembled into filaments in living cells are unknown.　We have revealed that most deposited alpha-synuclein in brains is highly phosphorylated at Ser129, suggesting that the hyperphosphorylation at Ser129 could be one of necessary factors for intracellular aggregation of alpha-synuclein.　Based on our and other observations, this review will discuss the function of alpha-synuclein and the molecular mechanisms to induce neuronal cell death by aggregated form in cells.

Address correspondence to Dr. Takashi Nonaka, Department of Molecular Neurobiology, Tokyo Institute of Psychiatry (2-1-8, Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan)