Role of mitogen-activated protein kinase inhibitors in Alzheimer's disease: Rouge of brain kinases

Abstract

Alzheimer's disease (AD) is the chief cause of dementia and related mortality worldwide due to progressive accumulation of amyloid peptide (Aβ) and hyperphosphorylated tau protein. These neuropathological changes lead to cognitive impairment and memory dysfunction. Notably, most Food drug Administration (FDA) approved anti-AD medications such as tacrine and donepezil are engaged with symptomatic relief of cognitive impairment but do not reverse the underlying AD neuropathology. Therefore, searching for new anti-AD is advisable. It has been shown that the inflammatory signaling pathways such as mitogen-activated protein kinases (MAPK) are intricate with the Aβ and tau protein neuropathology in AD. In addition, inhibition of brain MAPK plays a critical role in mitigating cognitive dysfunction in early-onset AD. Though, the fundamental mechanisms for the beneficial effects of MAPK inhibitors were not fully explained. Therefore, this review aims to discuss the potential molecular mechanisms of MAPK inhibitors in AD.