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The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of \u03b1S, among PD subtypes, and the potential relevance to therapy. Presumably, \u03b1S evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that \u03b1S prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of \u03b1S. Importantly, \u03b2-synuclein (\u03b2S), the nonamyloidogenic homologue of \u03b1S, might buffer against evolvability of \u03b1S protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased \u03b1S evolvability through suppression of \u03b2S expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand \u03b1S evolvability in PD pathogenesis, leading to rational therapy development.<\/jats:p>","DOI":"10.1155\/2021\/6318067","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T19:57:19Z","timestamp":1637697439000},"page":"1-11","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of \u03b1-Synuclein Evolvability for Autosomal Recessive Parkinson\u2019s Disease"],"prefix":"10.1155","volume":"2021","author":[{"given":"Jianshe","family":"Wei","sequence":"first","affiliation":[{"name":"Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"},{"name":"Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Ho","sequence":"additional","affiliation":[{"name":"PCND Neuroscience Research Institute, Poway 92064, CA, 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