A Comprehensive Investigation on the Role of Bioactives on DYRK1A to Avert Alzheimer’s Disease

DYRK1A belongs to the CMGC kinase group, which is an evolutionarily conserved family. A particular kind of gene situated in the 21q22.2 of the chromosome in the human domain encodes DYRK1A, which has garnered focus because it has been linked to neuropathological traits of people who have Down Syndrome (DS). Both DS and Alzheimer’s Disease (AD) cognitive dysfunctions are lessened in animal models when DYRK1A is inhibited. There are, at present, very few therapy options available for the cognitive deficits linked to AD as well as DS, which represents a significant unfulfilled therapeutic necessity. Pharmacological treatment for cognitive deficits connected to AD, along with various neurological disorders, might be attainable by inhibiting brain DYRK1A activity with small molecules. Here, we provide a comprehensive summary of DYRK1A’s role in the pathophysiology of AD along with details on its structure, function, and regulation. We also include a brief analysis of DYRK1A’s natural inhibitors, such as Aristolactam BIII, Epigallocatechin Gallate (EGCG), Harmine, along with marine compounds such as Meridianins, Leucettines that have a particular interaction with the ATP binding domain of DYRK1A, and their Structure-Activity Relationship (SAR) investigations. Major Findings: Natural DYRK1A inhibitors help reduce the cognitive dysfunctions observed in animal models by inhibiting DYRK1A. With an IC50 analogs of 580 nM, compound-7 i.e. 3-(2-amino-4-(3H-indol-3-yl) pyrimidin-5-yl) benzamide, showed the greatest inhibitory activity against DYRK1A of all the DYRK1A inhibitors discussed.