Role of cathepsins in Alzheimer's disease: A systematic review
Alzheimer's disease (AD) is a multifactorial disease. In addition to the precipitating of two proteins betaamyloid peptide and neurofebrillary tangles, which are the main mechanisms involved in the pathogenesis of
AD, other factors such as inflammatory mechanisms and changes in lysosomal enzymes play an important part in the pathogenesis of this disease. Increased and decreased lysosomal proteases, such as cathepsin, can lead to functional impairment and gradual death of neurons. The aim of this review was to investigate the role of cathepsins in the pathogenesis of AD. To conduct this review, relevant articles published between 2000 and 2016, and indexed in reliable databases including PubMed, Google Scholar, Scopus and Web of Science were retrieved. After reviewing the articles, 30 articles that directly addressed the subject of this review were included in final analysis. Cathepsins exacerbate intracellular conditions in neurons, by processing beta-amyloid precursor protein and converting it into amyloid beta. They also play a protective role against AD and fight it by catalyzing the decomposition of beta-amyloids and converting them into the cut out forms of the carboxyl C-terminus. In addition, the 24 kDa fragment resulting from the effect of cathepsin D on apolipoprotein E (ApoE) is the second binding to the receptor in the ApoE. This fragment may also be the cause of the pathogenicity of Apo E in AD. Identifying and explaining the mechanisms involved in the pathogenesis of AD can play a significant role in the prevention and treatment of this disease. Since cathepsins play a pivotal role in the decomposition of beta-amyloid and reduction of the risk of AD, further studies can be considered an effective approach to study AD.
Journal of Medical and Biomedical Sciences (2018) 7(1), 1 - 10