In:
Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 30, No. 6 ( 2023-02), p. 669-688
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0929-8673
DOI:
10.2174/0929867329666220620162018
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2023
SSG:
15,3
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