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Title: Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer's disease
Authors: Nalini Schaduangrat
Veda Prachayasittikul
Saowapak Choomwattana
Prapimpun Wongchitrat
Kamonrat Phopin
Wilasinee Suwanjang
Aijaz Ahmad Malik
Bruno Vincent
Chanin Nantasenamat
Mahidol University
CNRS Centre National de la Recherche Scientifique
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2019
Citation: Medicinal Research Reviews. Vol.39, No.5 (2019), 1730-1778
Abstract: © 2019 Wiley Periodicals, Inc. The continual increase of the aging population worldwide renders Alzheimer's disease (AD) a global prime concern. Several attempts have been focused on understanding the intricate complexity of the disease's development along with the on- andgoing search for novel therapeutic strategies. Incapability of existing AD drugs to effectively modulate the pathogenesis or to delay the progression of the disease leads to a shift in the paradigm of AD drug discovery. Efforts aimed at identifying AD drugs have mostly focused on the development of disease-modifying agents in which effects are believed to be long lasting. Of particular note, the secretase enzymes, a group of proteases responsible for the metabolism of the β-amyloid precursor protein (βAPP) and β-amyloid (Aβ) peptides production, have been underlined for their promising therapeutic potential. This review article attempts to comprehensively cover aspects related to the identification and use of drugs targeting the secretase enzymes. Particularly, the roles of secretases in the pathogenesis of AD and their therapeutic modulation are provided herein. Moreover, an overview of the drug development process and the contribution of computational (in silico) approaches for facilitating successful drug discovery are also highlighted along with examples of relevant computational works. Promising chemical scaffolds, inhibitors, and modulators against each class of secretases are also summarized herein. Additionally, multitarget secretase modulators are also taken into consideration in light of the current growing interest in the polypharmacology of complex diseases. Finally, challenging issues and future outlook relevant to the discovery of drugs targeting secretases are also discussed.
ISSN: 10981128
Appears in Collections:Scopus 2019

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