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A threshold value for accumulated neurotoxicity is estimated, beyond which neuron death is likely. Numerical results suggest that rapid deposition of \u03b1\u2010syn oligomers into fibrils minimizes neurotoxicity, indicating that the formation of Lewy bodies might play a neuroprotective role. Strategies such as reducing \u03b1\u2010syn monomer production or enhancing degradation can decrease accumulated neurotoxicity. In contrast, slower degradation (reflected by longer half\u2010lives of monomers and free aggregates) increases neurotoxicity, supporting the idea that impaired protein degradation may contribute to Parkinson's disease progression. Accumulated neurotoxicity is highly sensitive to the half\u2010deposition time of free \u03b1\u2010syn aggregates into fibrils, exhibiting a sharp increase as it transitions from negligible to elevated levels, indicative of neural damage.<\/jats:p>","DOI":"10.1002\/cnm.70027","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:15:39Z","timestamp":1745838939000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Criterion for Assessing Accumulated Neurotoxicity of Alpha\u2010Synuclein Oligomers in Parkinson's Disease"],"prefix":"10.1002","volume":"41","author":[{"given":"Andrey V.","family":"Kuznetsov","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133400"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-021-00273-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.15586\/codonpublications.parkinsonsdisease.2018.ch1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009399"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2854-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-802395-2.00024-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.3.245"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1913904117"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104876"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0423-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-020-00416-6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509567103"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2024.111734"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(04)00827-0"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brain.2020.100014"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0060860"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.aiht.2020.09.001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33252-6"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00408"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21937-3"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/imammb\/dqac006"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspa.2024.0652"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.4067701"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi701899y"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.7b00251"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemmater.0c00780"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcc.6b12021"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.12.4290"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/tpj.14534"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.12.018"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.03.015"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)95974-0"},{"key":"e_1_2_9_37_1","first-page":"155","volume-title":"Blue Books of Neurology","author":"Gupta A.","year":"2010"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.01.013"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300227200"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111732"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e03295"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-022-00939-w"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja8017412"},{"key":"e_1_2_9_44_1","volume-title":"Parameter Estimation in Science and Engineering","author":"Beck J. 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