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• W2889715260 endingPage "1128" @default.
• W2889715260 startingPage "1116" @default.
• W2889715260 abstract "In Parkinson's disease, the progressive neurodegeneration of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta (SNc) is associated with classic motor features, which typically have a focal onset. Since a defined somatotopic arrangement in the SNc has not been recognized, this focal motor onset is unexplained and hardly justified by current pathogenic theories of bottom-up disease progression (Braak's hypothesis, prionopathy). Here we propose that corticostriatal activity may represent a critical somatotopic stressor for nigrostriatal terminals, ultimately driving retrograde nigrostriatal degeneration and leading to focal motor onset and progression of Parkinson's disease. As a pathogenic mechanism, corticostriatal activity may promote secretion of striatal extracellular alpha-synuclein, favoring its pathological aggregation at vulnerable dopaminergic synapses. A similar pathogenic process may occur at corticofugal projections to the medulla oblongata and other vulnerable structures, thereby contributing to the bottom-up progression of Lewy pathology. This cortical pathogenesis may co-exist with bottom-up mechanisms, adding an integrative top-down perspective to the quest for the factors that impinge upon the vulnerability of dopaminergic cells in the onset and progression of Parkinson's disease." @default.
• W2889715260 created "2018-09-27" @default.
• W2889715260 creator A5047969875 @default.
• W2889715260 creator A5062838955 @default.
• W2889715260 date "2018-09-01" @default.
• W2889715260 modified "2023-10-12" @default.
• W2889715260 title "A Cortical Pathogenic Theory of Parkinson’s Disease" @default.
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