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The Oligomer Hypothesis in α-Synucleinopathy

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Abstract

Lewy bodies and Lewy neurites in the brain constitute the main histopathological features of Parkinson’s disease (PD) and dementia with Lewy bodies. They comprise amyloid-like fibrils composed of α-synuclein (αS), a small protein (~14 kDa). Because the aggregation of αS in the brain has been implicated as a critical step in the development of these diseases, the research for disease-modifying drugs has focused on modification of the αS aggregation process in the brain. Recent studies using synthetic αS peptides, a cell culture model, transgenic mice models, and human samples such as cerebrospinal fluids and the blood of PD patients have suggested that pre-fibrillar forms of αS (i.e., oligomers) are more critical than fibrillar forms (such as Lewy bodies) in the pathogenesis of α-synucleinopathies. Based on the accumulating evidence that oligomers play a central role in the pathogenesis of PD and other α-synucleinopathies (the “oligomer hypothesis”). This report reviews the recent findings regarding the oligomer hypothesis in the research of α-synucleinopathies.

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Acknowledgements

The authors thank Drs. M. Yamada, R. Takahashi, T. Ikeda, A. Morinaga, M. Noguchi-Shinohara, and T. Hamaguchi (Kanazawa University) for assistance in preparing the manuscript.

Funding

This study was supported by Grants-in-Aid for Young Scientists (B), Scientific Research (C) (26461266) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, a grant from Takeda Science Foundation, a grant from Nagao Memorial Foundation, and a grant from Life Science Foundation of Japan.

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  1. Department of Neurology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan

    Kenjiro Ono

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Ono, K. The Oligomer Hypothesis in α-Synucleinopathy. Neurochem Res 42, 3362–3371 (2017). https://doi.org/10.1007/s11064-017-2382-x

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