Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies
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 pro...
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doaj-89141edc7b1e4788af2bd8e58c40ebc52020-11-24T22:12:29ZengMDPI AGBiomolecules2218-273X2015-05-01521000101110.3390/biom5021000biom5021000Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related SynucleinopathiesAkio Sekigawa0Yoshiki Takamatsu1Kazunari Sekiyama2Makoto Hashimoto3Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, JapanTokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, JapanTokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, JapanTokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, JapanAxonal 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.http://www.mdpi.com/2218-273X/5/2/1000axonopathiesα-synucleinopathiesParkinson’s disease (PD)dementia with Lewy bodies (DLB)transgenic (tg)globules |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Akio Sekigawa Yoshiki Takamatsu Kazunari Sekiyama Makoto Hashimoto |
spellingShingle |
Akio Sekigawa Yoshiki Takamatsu Kazunari Sekiyama Makoto Hashimoto Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies Biomolecules axonopathies α-synucleinopathies Parkinson’s disease (PD) dementia with Lewy bodies (DLB) transgenic (tg) globules |
author_facet |
Akio Sekigawa Yoshiki Takamatsu Kazunari Sekiyama Makoto Hashimoto |
author_sort |
Akio Sekigawa |
title |
Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies |
title_short |
Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies |
title_full |
Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies |
title_fullStr |
Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies |
title_full_unstemmed |
Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies |
title_sort |
role of α- and β-synucleins in the axonal pathology of parkinson’s disease and related synucleinopathies |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2015-05-01 |
description |
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. |
topic |
axonopathies α-synucleinopathies Parkinson’s disease (PD) dementia with Lewy bodies (DLB) transgenic (tg) globules |
url |
http://www.mdpi.com/2218-273X/5/2/1000 |
work_keys_str_mv |
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