Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches.
Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches.
复制标题
阿尔茨海默病及相关疾病的脑胰岛素抵抗：机制和治疗方法。
DOI：
10.1016/s1474-4422(20)30231-3
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发表时间：
2020-09
期刊：
影响因子：
48
通讯作者：
Craft, Suzanne
中科院分区：
文献类型：
--
作者：
Kellar, Derek;Craft, Suzanne
胰岛素是胰腺分泌的一种肽，在外周组织葡萄糖代谢的调节中起重要作用。虽然胰岛素在外周中的作用已被充分理解，但对其在大脑中的多因素作用知之甚少。然而，来自人类和动物研究的新证据表明，胰岛素影响大脑生物能量学，增强突触活力和树突棘形成，并增加神经递质（如多巴胺）的周转。胰岛素还在蛋白质稳定中起作用，影响淀粉样β肽的清除和tau的磷酸化，这是阿尔茨海默病的标志。胰岛素还通过影响血管反应性、脂质代谢和炎症来调节血管功能。通过这些多种途径，胰岛素失调可能导致神经退行性变。因此，正在研究恢复脑胰岛素功能的新方法，这些方法可以为患有阿尔茨海默病、血管性认知障碍或相关疾病的成年人提供治疗益处。
Insulin is a peptide secreted by the pancreas and plays an important role in the regulation of glucose metabolism in peripheral tissues. Although the role of insulin in the periphery is well understood, less is known about its multifactorial role in the brain. However, emerging evidence from human and animal studies indicate that insulin influences cerebral bioenergetics, enhances synaptic viability and dendritic spine formation, and increases turnover of neurotransmitters, such as dopamine. Insulin also has a role in proteostasis, influencing clearance of the amyloid β peptide and phosphorylation of tau, which are hallmarks of Alzheimer’s disease. Insulin also modulates vascular function through effects on vasoreactivity, lipid metabolism, and inflammation. Through these multiple pathways, insulin dysregulation could contribute to neurodegeneration. Thus, new approaches to restore cerebral insulin function that could offer therapeutic benefit to adults with Alzheimer’s disease, vascular cognitive impairment, or related disorders are being investigated.