Role of mitogen-activated protein kinase inhibitors in Alzheimer's disease: Rouge of brain kinases
Suad Hamdan Almasoudi, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb, Duaa Eliwa, Αθανάσιος Αλεξίου, Marios Papadakis, Gaber El‐Saber Batiha
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. • AD is the chief cause of dementia and related due to progressive accumulation of Aβ and hyperphosphorylated tau protein. • Many studies confirmed that exaggerated MAPK pathway in response to the accumulated Aβ and hyperphosphorylated tau protein is involved in neuronal apoptosis and the progression of AD neuropathology. • Findings from preclinical studies indicated that MAPK inhibitors can reduce neurotoxicity, neuronal apoptosis, inflammation, and oxidative stress in AD. Nonetheless, these experimental agents did not enter the clinical trials and not available for clinical use in AD. • Overall, MAPK pathway is implicated in the pathogenesis of AD by increasing the accumulation of Aβ and tau protein