Crosstalk between death-associated protein kinase 1-regulated mechanisms and dysfunctions in alzheimer's disease.

Alzheimer's disease (AD) is a chronic progressive neurocognitive disorder manifested by increased production and deposition of amyloid beta (Aβ), abnormal tau phosphorylation, and formation of neurofibrillary tangles (NFTs). In addition, the disease progression is found to be associated with neuronal cell death, elevated levels of reactive oxygen species, mitochondrial dysfunction, and loss of synaptic plasticity in specific regions of the brain. AD is seventh leading cause of death and over more than 70%-80% of 57 million people having dementia develop AD worldwide. The disease population is also severely increasing at an alarming rate globally. The currently available treatment strategies remain insufficient to cure the disease because AD involves very complex pathways during its progression. Death-associated protein kinase 1 (DAPK1) is identified as a promising next-generation therapeutic drug target for the management of AD. It belongs to a family of serine/threonine kinases that influences different hypotheses involved in AD pathogenesis, such as tauopathies, Aβ hypothesis, redox, and autophagy pathways. In this review, we highlight the involvement of DAPK1 in various molecular pathways associated with AD pathogenesis and the crosstalk between DAPK1 and synaptic dysfunction and neuronal cell death implicated in AD. Moreover, the various small molecules, microRNAs, and phytoconstituents have been discussed, which have the potential to be developed as a treatment strategy targeting DAPK1-related pathological pathways in AD.