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Comput. Neurosci."],"abstract":"<jats:p>Accumulation of the misfolded synaptic protein \u03b1-synuclein (\u03b1Syn<jats:sup>*<\/jats:sup>) is a hallmark of neurodegenerative disease in Parkinson's disease (PD). Recent studies suggest that the autophagy lysosome pathway (ALP) including both the Beclin1-associated and mTOR-signaling pathways is involved in the \u03b1Syn<jats:sup>*<\/jats:sup> clearance mechanism. In this study, a mathematical model is proposed for the degradation of \u03b1Syn<jats:sup>*<\/jats:sup> by ALP with the crosstalk element of mTOR. Using codimension-1 bifurcation analysis, the tri-stability of \u03b1Syn<jats:sup>*<\/jats:sup> is surveyed under three different stress signals and, in addition, consideration is given to the regulatory mechanisms for the Beclin1- and mTOR-dependent rates on \u03b1Syn<jats:sup>*<\/jats:sup> degradation using the codimension-1 and\u22122 bifurcation diagrams. It was found that, especially under internal and external oxidative stresses (<jats:italic>S<\/jats:italic><jats:sub>1<\/jats:sub>), the bistable switch of the aggregation of \u03b1Syn<jats:sup>*<\/jats:sup> can be transformed from an irreversible to a reversible condition through the ALP degradation pathways. Furthermore, the robustness of the tri-stable state for the stress <jats:italic>S<\/jats:italic><jats:sub>1<\/jats:sub> to the parameters related to mTOR-mediated ALP was probed. It was confirmed that mTOR-mediated ALP is important for maintaining the essential dynamic features of the tri-stable state. This study may provide a promising avenue for conducting further experiments and simulations of the degradation mechanism of dynamic modeling in PD.<\/jats:p>","DOI":"10.3389\/fncom.2023.1068150","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T04:32:04Z","timestamp":1681360324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Dynamics of a model for the degradation mechanism of aggregated \u03b1-synuclein in Parkinson's disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Bojie","family":"Yang","sequence":"first","affiliation":[]},{"given":"Zhuoqin","family":"Yang","sequence":"additional","affiliation":[]},{"given":"Lijie","family":"Hao","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.neurobiolaging.2020.12.013","article-title":"Can the interplay between autophagy and apoptosis be targeted as a novel therapy for Parkinson's disease?","volume":"100","author":"Bekker","year":"2021","journal-title":"Neurobiol. 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