Department of Pharmacy, Birla Institute of Technology and Science, Pilani-333031, Rajasthan, India.
Curr Pharm Des. 2019;25(23):2555-2568. doi: 10.2174/1381612825666190716101411.
Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer's Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.
神经退行性疾病是神经系统最具破坏性的疾病。神经退行性变的病理基础与功能失调的蛋白质运输、线粒体应激、环境因素和衰老有关。随着某些大脑部位胰岛素和胰岛素受体的鉴定，很明显，某些与胰岛素功能障碍相关的代谢状况，如 2 型糖尿病（T2DM）、血脂异常、肥胖症等，也被认为是导致神经退行性变的原因，主要是阿尔茨海默病（AD）。最近，成纤维细胞生长因子（FGF）超家族的一个成员，FGF21 在糖尿病、肥胖症和胰岛素抵抗（IR）等疾病中已被证明具有巨大的疗效。据报道，FGF21 水平升高在代谢综合征中发挥多种有益作用。FGF21 受体存在于大脑中与学习和记忆有关的某些区域。然而，尽管进行了广泛的研究，但其在 AD 中的神经保护作用仍然难以捉摸。FGF21 是一种循环内分泌激素，主要由肝脏在禁食状态下分泌。FGF21 通过与 FGFR1 和共同受体β-klotho（KLB）结合发挥作用。它参与通过葡萄糖和脂质代谢来调节能量。人们认为异常的 FGF21 信号可能导致各种异常，如神经退行性变、癌症、代谢功能障碍等。因此，本综述将主要关注 FGF21 作为神经保护剂和潜在代谢调节剂的作用。此外，我们还将回顾其作为新兴候选药物对抗代谢应激诱导的神经退行性异常的潜力。
