Sharma Tanya, Kaur Darshpreet, Grewal Amarjot Kaur, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Neurosci Lett. 2021 Apr 1;749:135754. doi: 10.1016/j.neulet.2021.135754. Epub 2021 Feb 18.
Parkinson's disease (PD) is a neurodegenerative disorder linked with aging and primarily involves dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc). The deregulation of genes associated with T2D has been demonstrated by proteomic research on Parkinson's symptoms patients. Various common pathways likely to link neurodegenerative mechanisms of PD include abnormal mitochondrial function, inflammation, apoptosis/autophagy and insulin signalling/glucose metabolism in T2DM. Several pathway components including phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), glycogen synthase kinase-3 beta (GSK-3β) and nuclear factor kappa B (NF-κB) impairment is observed in PD. Numerous novel targets are being pursued in preclinical and clinical trials that target metabolic dysfunction in PD; that elevate insulin signaling pathways in dopaminergic neurons, and show improvement in motor and cognitive measures and produce significant neuroprotective effects in PD patients.
帕金森病(PD)是一种与衰老相关的神经退行性疾病,主要涉及黑质致密部(SNpc)中多巴胺能神经元的丧失。对帕金森病症状患者的蛋白质组学研究表明,与2型糖尿病相关的基因失调。可能将帕金森病神经退行性机制联系起来的各种常见途径包括2型糖尿病中线粒体功能异常、炎症、细胞凋亡/自噬以及胰岛素信号传导/葡萄糖代谢。在帕金森病中观察到包括磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)、糖原合酶激酶-3β(GSK-3β)和核因子κB(NF-κB)损伤在内的几种途径成分受损。在临床前和临床试验中正在探索许多针对帕金森病代谢功能障碍的新靶点;这些靶点可提高多巴胺能神经元中的胰岛素信号通路,并在帕金森病患者中改善运动和认知指标并产生显著的神经保护作用。
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