Pardeshi Rohit, Bolshette Nityanand, Gadhave Kundlik, Ahire Ashutosh, Ahmed Sahabuddin, Cassano Tommaso, Gupta Veer Bala, Lahkar Mangala
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati 781032, Assam, India.
Institutional Level Biotech hub (IBT hub), Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati 781032, Assam, India.
Psychoneuroendocrinology. 2017 Sep;83:159-171. doi: 10.1016/j.psyneuen.2017.05.004. Epub 2017 May 30.
Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by accumulation of senile plaques, neurofibrillary tangles (NFT) and neurodegeneration. The diabetes mellitus (DM) is one of the risk factors for AD pathogenesis by impairment in insulin signaling and glucose metabolism in central as well as peripheral system. Insulin resistance, impaired glucose and lipid metabolism are leading to the Aβ (Aβ) aggregation, Tau phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, memory impairment and also mark over Aβ transport through central to peripheral and vice versa. Several pathways, like enzymatic degradation of Aβ, forkhead box protein O1 (FOXO) signaling, insulin signaling shared common pathological mechanism for both AD and DM. Recent evidence showed that hyperinsulinemia and hyperglycemia affect the onset and progression of AD differently. Some researchers have suggested that hyperglycemia influences vascular tone, while hyperinsulinemia may underlie mitochondrial deficit. The objective of this review is to determine whether existing evidence supports the concept that impairment in insulin signaling and glucose metabolism play an important role in pathogenesis of AD. In the first part of this review, we tried to explain the interconnecting link between AD and DM, whereas the second part includes more information on insulin resistance and its involvement in AD pathogenesis. In the final part of this review, we have focused more toward the AD treatment by targeting insulin signaling like anti-diabetic, antioxidant, nutraceuticals and dietary supplements. To date, more researches should be done in this field in order to explore the pathways in insulin signaling, which might ameliorate the treatment options and reduce the risk of AD due to DM.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为老年斑、神经原纤维缠结（NFT）的积累以及神经退行性变。糖尿病（DM）是AD发病机制的危险因素之一，可通过中枢和外周系统的胰岛素信号传导及葡萄糖代谢受损导致发病。胰岛素抵抗、葡萄糖和脂质代谢受损会导致β淀粉样蛋白（Aβ）聚集、 Tau蛋白磷酸化、线粒体功能障碍、氧化应激、蛋白质错误折叠、记忆障碍，还会影响Aβ在中枢和外周之间的转运，反之亦然。一些途径，如Aβ的酶促降解、叉头框蛋白O1（FOXO）信号传导、胰岛素信号传导，是AD和DM共同的病理机制。最近的证据表明，高胰岛素血症和高血糖对AD的发病和进展有不同影响。一些研究人员认为，高血糖影响血管张力，而高胰岛素血症可能是线粒体缺陷的基础。本综述的目的是确定现有证据是否支持胰岛素信号传导和葡萄糖代谢受损在AD发病机制中起重要作用这一概念。在本综述的第一部分，我们试图解释AD和DM之间的相互联系，而第二部分包含更多关于胰岛素抵抗及其在AD发病机制中的作用的信息。在本综述的最后一部分，我们更侧重于通过靶向胰岛素信号传导进行AD治疗，如使用抗糖尿病药物、抗氧化剂、营养保健品和膳食补充剂。迄今为止，该领域应开展更多研究，以探索胰岛素信号传导途径，这可能会改善治疗方案并降低因DM导致AD的风险。
