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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease

Author(s): Márcia Maria de Souza, Arthur Ribeiro Cenci, Kerolain Faoro Teixeira, Valkiria Machado, Majory Christina Garcia Mendes Schuler, Ana Elisa Gonçalves, Ana Paula Dalmagro, Camila André Cazarin, Leonardo Luiz Gomes Ferreira, Aldo Sena de Oliveira and Adriano Defini Andricopulo*

Volume 30, Issue 6, 2023

Published on: 29 August, 2022

Page: [669 - 688] Pages: 20

DOI: 10.2174/0929867329666220620162018

Price: $65


Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most common form of dementia, especially in the elderly. Due to the increase in life expectancy, in recent years, there has been an excessive growth in the number of people affected by this disease, causing serious problems for health systems. In recent years, research has been intensified to find new therapeutic approaches that prevent the progression of the disease. In this sense, recent studies indicate that the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and overexpressed in Down syndrome (DS), may play a significant role in developmental brain disorders and early onset neurodegeneration, neuronal loss and dementia in DS and AD. Inhibiting DYRK1A may serve to stop the phenotypic effects of its overexpression and, therefore, is a potential treatment strategy for the prevention of ageassociated neurodegeneration, including Alzheimer-type pathology.

Objective: In this review, we investigate the contribution of DYRK1A inhibitors as potential anti-AD agents.

Methods: A search in the literature to compile an in vitro dataset including IC50 values involving DYRK1A was performed from 2014 to the present day. In addition, we carried out structure-activity relationship studies based on in vitro and in silico data.

Results: molecular modeling and enzyme kinetics studies indicate that DYRK1A may contribute to AD pathology through its proteolytic process, reducing its kinase specificity.

Conclusion: further evaluation of DYRK1A inhibitors may contribute to new therapeutic approaches for AD.

Keywords: Alzheimer’s disease, neurodegeneration, protein kinases, enzyme kinetics, DYRK1A inhibitors, molecular docking.

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