Role of insulin resistance in Alzheimer's disease.
A critical role of insulin resistance (IR) in Alzheimer's disease (AD) includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles (NFTs), failure of synaptic transmission and neuronal degeneration. Aβ is sequentially cleavaged from APP by two proteolytic enzymes: β-secretase and γ-secretase. IR could regulate Aβ production via enhancing β- and γ-secretase activity. Meanwhile, IR induces oxidative stress and inflammation in the brain which contributes to Aβ and tau pathology. Aβ accumulation can enhance IR through Aβ-mediated inflammation and oxidative stress. IR is a possible linking between amyloid plaques and NFTs pathology via oxidative stress and neuroinflammation. Additionally, IR could disrupt acetylcholine activity, and accelerate axon degeneration and failures in axonal transport, and lead to cognitive impairment in AD. Preclinical and clinical studies have supported that insulin could be useful in the treatment of AD. Thus, an effective measure to inhibit IR may be a novel drug target in AD.
Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, No. 39 Chaoyang Middle Road, Shiyan, 442000, Hubei Province, People's Republic of China, c0909@hotmail.com.
Zhiyou
Z
Cai
Ming
M
Xiao
Liying
L
Chang
Liang-Jun
LJ
Yan
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D016875:tau Proteins / Q000009:adverse effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins