Unravelling the Alzheimer's pathogenesis: Molecular and cellular pathways to neurodegeneration and therapeutic targets

Alzheimer's disease (AD) is indeed a overwhelming neurodegenerative disorder whose intricated pathogenesis still remains exclusive and requires to be completely elucidated. This review undertakes a comprehensive analysis of the multifactorial signaling mechanism implicated in AD, such as AKT/MAPK, Wnt, Leptin, mTOR, ubiquitin, Sirt1, and insulin, exploring their pivotal individual and/or synergistic contribution in the dysregulation of diverse cellular processes accountable for neuronal health. Furthermore, it also delves into the molecular and cellular mechanism underlying oxidative stress, neuroinflammation, apoptosis, metal ion dyshomeostasis, and viral reactivation in the pathogenesis of AD, along with accentuating the interconnection between the intracellular signalling cascades and the alterations within the synaptic transmission, blood-brain barrier, and gut microbiota. Nevertheless, due to the enormous complexity of the brain, the application of these several signaling pathways as feasible targets for drug development against AD is minimal. This review also explores the numerous drug candidates, both synthetic and natural, currently being investigated for their anti-AD potential via targeting diverse pathological hallmark of AD and their associated signalling mechanisms. Ultimately, this review seeks to stimulate further research into these promising "anti-AD pathways" and to accelerate the expansion of disease-modifying therapies.