Jurnal Internasional Tersangka yang biasa, dopamin dan alpha-synuclein, bersekongkol untuk menyebabkan neurodegenerasi – Mor – Gangguan Gerakan

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Jurnal Internasional Tersangka yang biasa, dopamin dan alpha-synuclein, bersekongkol untuk menyebabkan neurodegenerasi – Mor – Gangguan Gerakan

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Parkinson's disease (PD) is primarily a movement disorder that is driven by the loss of dopamine-producing neurons in the substantia nigra (SN). Early identification of the oxidative nature of dopamine implies it is a potential source of oxidative stress in PD, but several studies have investigated dopamine neurotoxicity in vivo. The discovery of mutations that cause PD in α-synuclein and the presence of α-synuclein aggregates in the typical Lewy body pathology of PD revealed other important players. Despite extensive efforts, the exact role of α-synuclein aggregation in neurodegeneration remains unclear. We recently manipulated dopamine levels and α-synuclein expression in old mice and found that only a combination of these 2 factors led to progressive SN neurodegeneration and associated motor deficits. Dopamine-modified α-synuclein aggregation in SN, results in a greater α-synuclein oligomer and unique dopamine-induced oligomeric conformation. Furthermore, disruption of dopamine α-synuclein interactions saved dopaminergic neurons from degeneration in the transgenic model Caenorhabditis elegans . In this perspective, we discuss these findings in the biological context of known α-synuclein and dopamine, examining evidence of the toxicity of α-synuclein oligomers and potential mechanisms, and discuss therapeutic implications. © 2019 International Parkinson and Movement Disorder Society

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