ADAM10: α-secretase in Alzheimer’s disease and regulator of neurobiology
Tóm tắt
Proteolytic and amyloidogenic processing of amyloid precursor protein (APP) by β- and γ-secretases are pathological hallmarks of Alzheimer’s disease (AD). These proteolytic activities lead to release of the amyloid-β peptides believed to cause neurological pathology and be linked to pathological progression in AD. Due to its capability to cleave APP within the toxic peptide sequence, the metalloproteinase ADAM10 (“a disintegrin and metalloprotease”) is a known antagonist of the disease-causing pathway. ADAM10 also plays a major role in the ectodomain shedding of a number of important cell surface proteins. In addition, ADAM10 is involved in the proteolytic activation cascade of the Notch receptor, which is of crucial function in developmental processes. The study of ADAM10-deficient mice also revealed that ADAM10 regulates synaptic function and synaptogenesis. Pharmacological activation of ADAM10 is postulated to represent a valuable strategy for prevention of AD. However, due to the multiple roles of ADAM10 in the brain, it will be challenging to find a suitable therapeutic window.
Tài liệu tham khảo
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