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Biomolecules 2015, 5(2), 1000-1011; doi:10.3390/biom5021000

Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies

Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Stephan N. Witt
Received: 7 April 2015 / Revised: 1 May 2015 / Accepted: 12 May 2015 / Published: 19 May 2015
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Abstract

Axonal swellings are histological hallmarks of axonopathies in various types of disorders in the central nervous system, including neurodegenerative diseases. Given the pivotal role of axonopathies during the early phase of neurodegenerative process, axonal swellings may be good models which may provide some clues for early pathogenesis of α-synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies (DLB). In this mini-review, such a possibility is discussed based on our recent studies as well as other accumulating studies. Consistent with the current view that dysfunction in the autophagy-lysosomal system may play a major role in the formation of axonal swellings, our studies showed globule, small axonal swellings, derived from transgenic mice expressing either human wild-type α-synuclein (αS-globule) or DLB-linked P123H β-synuclein (βS-globule), contained autophagosome-like membranes. However, other pathological features, such as abnormal mitochondria, enhanced oxidative stress and LRRK2 accumulation, were observed in the αS-globules, but not in the βS-globules. Collectively, it is predicted that αS and βS may be involved in axonopathies through similar but distinct mechanisms, and thus, contribute to diverse axonal pathologies. Further studies of the axonal swellings may lead to elucidating the pathogenic mechanism of early α-synucleinopathies and illuminating a strategy for a disease-modifying therapy against these devastating disorders. View Full-Text
Keywords: axonopathies; α-synucleinopathies; Parkinson’s disease (PD); dementia with Lewy bodies (DLB); transgenic (tg); globules axonopathies; α-synucleinopathies; Parkinson’s disease (PD); dementia with Lewy bodies (DLB); transgenic (tg); globules
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sekigawa, A.; Takamatsu, Y.; Sekiyama, K.; Hashimoto, M. Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies. Biomolecules 2015, 5, 1000-1011.

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