Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Its major pathological hallmarks, neurofibrillary tangles (NFT), and amyloid-β plaques can result from dysfunctional insulin signaling. Insulin is an important growth factor that regulates cell growth, energy utilization, mitochondrial function, autophagy, oxidative stress, synaptic plasticity, and cognitive function. Insulin and its downstream signaling molecules are located majorly in the regions of cortex and hippocampus. The major molecules involved in impaired insulin signaling include IRS, PI3K, Akt, and GSK-3β. Activation or inactivation of these major molecules through increased or decreased phosphorylation plays a role in insulin signaling abnormalities or insulin resistance. Insulin resistance, therefore, is considered as a major culprit in generating the hallmarks of AD arising from neuroinflammation and oxidative stress, etc. Moreover, caspases, Nrf2, and NF-κB influence this pathway in an indirect way. Various studies also suggest a strong link between Diabetes Mellitus and AD due to the impairment of insulin signaling pathway. Moreover, studies also depict a strong correlation of other neurodegenerative diseases such as Parkinson's disease and Huntington's disease with insulin resistance. Hence this review will provide an insight into the role of insulin signaling pathway and related molecules as therapeutic targets in AD and other neurodegenerative diseases.

中文翻译：

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胰岛素信号传导途径和相关分子：在神经变性和阿尔茨海默氏病中的作用。

阿尔茨海默氏病（AD）是最常见的神经退行性疾病之一。它的主要病理标志，神经原纤维缠结（NFT）和淀粉样蛋白-β斑块可能是由胰岛素信号传导异常引起的。胰岛素是调节细胞生长，能量利用，线粒体功能，自噬，氧化应激，突触可塑性和认知功能的重要生长因子。胰岛素及其下游信号分子主要位于皮质和海马区。胰岛素信号转导受损的主要分子包括IRS，PI3K，Akt和GSK-3β。这些主要分子通过增加或减少的磷酸化激活或失活在胰岛素信号异常或胰岛素抵抗中起作用。因此，胰岛素抵抗 被认为是造成神经炎症和氧化应激等引起的AD标志的罪魁祸首。此外，胱天蛋白酶，Nrf2和NF-κB间接影响该途径。各种研究还表明，由于胰岛素信号通路的损伤，糖尿病与AD之间存在密切联系。此外，研究还描述了其他神经退行性疾病（如帕金森氏病和亨廷顿氏病）与胰岛素抵抗的密切相关。因此，本综述将提供有关胰岛素信号通路和相关分子作为AD和其他神经退行性疾病治疗靶标的作用的见解。各种研究还表明，由于胰岛素信号通路的损伤，糖尿病与AD之间存在密切联系。此外，研究还描述了其他神经退行性疾病（如帕金森氏病和亨廷顿氏病）与胰岛素抵抗的密切相关。因此，本综述将提供有关胰岛素信号通路和相关分子作为AD和其他神经退行性疾病治疗靶标的作用的见解。各种研究还表明，由于胰岛素信号通路的损伤，糖尿病与AD之间存在密切联系。此外，研究还描述了其他神经退行性疾病（如帕金森氏病和亨廷顿氏病）与胰岛素抵抗的密切相关。因此，本综述将提供有关胰岛素信号通路和相关分子作为AD和其他神经退行性疾病治疗靶点的作用的见解。