Rapamycin Responds to Alzheimer’s Disease: A Potential Translational Therapy
Si-Jia Hou, Sheng‐Xiao Zhang, Li Yang, Sui-yi Xu
Abstract
Abstract: Alzheimer’s disease (AD) is a sporadic or familial neurodegenerative disease of insidious onset with progressive cognitive decline. Although numerous studies have been conducted or are underway on AD, there are still no effective drugs to reverse the pathological features and clinical manifestations of AD. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus . As a classical mechanistic target of rapamycin (mTOR) inhibitor, rapamycin has been shown to be beneficial in a variety of AD mouse and cells models, both before the onset of disease symptoms and the early stage of disease. Although many basic studies have demonstrated the therapeutic effects of rapamycin in AD, many questions and controversies remain. This may be due to the variability of experimental models, different modes of administration, dose, timing, frequency, and the availability of drug-targeting vehicles. Rapamycin may delay the development of AD by reducing β-amyloid (Aβ) deposition, inhibiting tau protein hyperphosphorylation, maintaining brain function in APOE ϵ4 gene carriers, clearing chronic inflammation, and improving cognitive dysfunction. It is thus expected to be one of the candidates for the treatment of Alzheimer’s disease. Keywords: β-amyloid, chronic inflammation, therapeutic effect, macrolide antibiotic