{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:15:56Z","timestamp":1792134956376,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 \u03b1-synucleinopathies, including Parkinson\u2019s 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 \u03b1-synuclein (\u03b1S-globule) or DLB-linked P123H \u03b2-synuclein (\u03b2S-globule), contained autophagosome-like membranes. However, other pathological features, such as abnormal mitochondria, enhanced oxidative stress and LRRK2 accumulation, were observed in the \u03b1S-globules, but not in the \u03b2S-globules. Collectively, it is predicted that \u03b1S and \u03b2S 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 \u03b1-synucleinopathies and illuminating a strategy for a disease-modifying therapy against these devastating disorders.<\/jats:p>","DOI":"10.3390\/biom5021000","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T10:35:57Z","timestamp":1432031757000},"page":"1000-1011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role of \u03b1- and \u03b2-Synucleins in the Axonal Pathology of Parkinson\u2019s Disease and Related Synucleinopathies"],"prefix":"10.3390","volume":"5","author":[{"given":"Akio","family":"Sekigawa","sequence":"first","affiliation":[{"name":"Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Takamatsu","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunari","family":"Sekiyama","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson\u2019s disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/j.1750-3639.1999.tb00552.x","article-title":"Alpha-synuclein in Lewy body disease and alzheimer\u2019s disease","volume":"9","author":"Hashimoto","year":"1999","journal-title":"Brain Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/sj.cdd.4400432","article-title":"Fatal attractions: Abnormal protein aggregation and neuron death in Parkinson\u2019s disease and Lewy body dementia","volume":"5","author":"Trojanowski","year":"1998","journal-title":"Cell Death Differ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0070-2153(04)60002-0","article-title":"Alpha-synuclein: Normal function and role in neurodegenerative diseases","volume":"60","author":"Norris","year":"2004","journal-title":"Curr. 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