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The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (\u03b1Syn)-rich Lewy bodies both manifesting with classical motor signs. \u03b1Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considered prevalent among individuals prior to PD diagnosis and persisting throughout the patient\u2019s life. NMS mainly includes loss of taste and smell, constipation, psychiatric disorders, dementia, impaired rapid eye movement (REM) sleep, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings on the impact of \u03b1Syn deposits on several prodromal NMS and emphasizes the importance of early detection of \u03b1Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.<\/jats:p>","DOI":"10.3390\/cells13151265","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T07:54:03Z","timestamp":1722239643000},"page":"1265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Alpha Synuclein Toxicity and Non-Motor Parkinson\u2019s"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5461-6837","authenticated-orcid":false,"given":"Gabriella M.","family":"Mazzotta","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2456-6300","authenticated-orcid":false,"given":"Carmela","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6682","DOI":"10.1038\/s41598-020-63412-x","article-title":"\u03b1-Synuclein Inclusions Are Abundant in Non-Neuronal Cells in the Anterior Olfactory Nucleus of the Parkinson\u2019s Disease Olfactory Bulb","volume":"10","author":"Stevenson","year":"2020","journal-title":"Sci. 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