The Structure and Function of α, β and γ-Secretase as Therapeutic Target Enzymes in the Development of Alzheimer’s Disease: A Review

Author(s): Syed S. Ahmad*, Shahzad Khan, Mohammad A. Kamal, Umam Wasi.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 18 , Issue 9 , 2019

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Graphical Abstract:


Abstract:

Alzheimer's disease is a progressive neurodegenerative disorder that affects the central nervous system. There are several factors that cause AD, like, intracellular hyperphosphorylated Tau tangles, collection of extracellular Amyloid-β42 and generation of reactive oxygen species due to mitochondrial dysfunction. This review analyses the most active target of AD and both types of AD-like early-onset AD and late-onset AD. BACE1 is a β-secretase involved in the cleavage of amyloid precursor protein and the pathogenesis of Alzheimer's disease. The presenilin proteins play a critical role in the pathogenesis of Alzheimer malady by intervening the intramembranous cleavage of amyloid precursor protein and the generation of amyloid β. The two homologous proteins PS1 and PS2 speak to the reactant subunits of particular γ-secretase edifices that intercede an assortment of cellular processes. Natural products are common molecular platforms in drug development in AD. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target in AD. Presently, there are a few theories clarifying the early mechanisms of AD pathogenesis. Recently, research advancements in the field of nanotechnology, which utilize macromolecular strategies to make drugs in nanoscale measurements, offer nanotechnology-based diagnostic tools and drug carriers which are highly sensitive for effective drug targeting in the treatment of Alzheimer’s disease.

Keywords: Alzheimer's disease, secretase activity, nanotechnology, BBB, APP, treatment.

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VOLUME: 18
ISSUE: 9
Year: 2019
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DOI: 10.2174/1871527318666191011145941
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