Çamoğlu Tugay, Yurttaş Zuhal, Kına Ümit Yaşar, Akkuş Süt Pınar, Sahin Fikrettin, Dursun Erdinç, Gezen-Ak Duygu
Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey.
Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34093, Turkey.
ACS Omega. 2024 Apr 4;9(15):17185-17194. doi: 10.1021/acsomega.3c10036. eCollection 2024 Apr 16.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. According to the Braak hypothesis, the disease spreads along specific neuroanatomical pathways. Studies indicate that fibrillar alpha-synuclein (F-αSyn) can propagate from cell-to-cell by following intercellular connections, leading to the selective death of certain cell groups like substantia nigra dopaminergic neurons and advancing the pathology. Internalized F-αSyn can be eliminated by lysosomes, proteasomes, or chaperones before it replicates inside the cell. Research has shown that F-αSyn can somehow escape from endosomes, lysosomes, and proteasomes and replicate itself. However, the impact of chaperones on intracellular levels during the initial hours of their internalization remains unknown. The present study investigates the effect of F-αSyn on chaperone levels within the first 6 and 12 h after internalization. Our findings showed that within the first 6 h, Hsc70 and Hsp90 levels were increased, while within 12 h, F-αSyn leads to a decrease or suppression of numerous intracellular chaperone levels. Exploring the pathological effects of PD on cells will contribute to identifying more targets for therapeutic interventions.
帕金森病（PD）是全球第二常见的神经退行性疾病。根据布拉克假说，该疾病沿特定神经解剖学途径传播。研究表明，纤维状α-突触核蛋白（F-αSyn）可通过细胞间连接在细胞间传播，导致黑质多巴胺能神经元等特定细胞群的选择性死亡，并推动病理进程。内化的F-αSyn在细胞内复制之前可被溶酶体、蛋白酶体或分子伴侣清除。研究表明，F-αSyn能以某种方式从内体、溶酶体和蛋白酶体中逃逸并自我复制。然而，分子伴侣在其内化最初数小时内对细胞内水平的影响尚不清楚。本研究调查了内化后最初6小时和12小时内F-αSyn对分子伴侣水平的影响。我们的研究结果表明，在最初6小时内，Hsc70和Hsp90水平升高，而在12小时内，F-αSyn导致多种细胞内分子伴侣水平降低或受到抑制。探索帕金森病对细胞的病理影响将有助于确定更多的治疗干预靶点。
