Exploring complexities of Alzheimer’s disease: New insights into molecular and cellular mechanisms of neurodegeneration and targeted therapeutic interventions

Abstract

Alzheimer’s disease (AD), the common form of dementia globally, is a complex condition including neurodegeneration; shares incompletely known pathogenesis. Signal transduction and biological activities, including cell metabolism, growth, and death are regulated by different signaling pathways including AKT/MAPK, Wnt, Leptin, mTOR, ubiquitin, Sirt1, and insulin. Absolute evidence linking specific molecular pathways with the genesis and/or progression of AD is still lacking. Changes in gut microbiota and blood-brain barrier also cause amyloid β aggregation in AD. The current review reports significant characteristics of various signaling pathways, their relationship with each other, and how they interact in disease genesis and/or progression. Nevertheless, due to the enormous complexity of the brain and numerous chemical linkages between these pathways, the use of signaling pathways as possible targets for drug development against AD is minimal. Currently, there is no permanent cure for AD, and there is no way to stop brain cell loss. This review also aimed to draw attention to the role of a novel group of signaling pathways, which can be collectively dubbed "anti-AD pathways", in multi-target therapy for AD, where cellular metabolic functions are severely impaired. Thus, different hypotheses have been formulated and elaborated to explain the genesis of AD, which can be further explored for drug development too.

keywords: 4S-hydroxycholesterol, Acetylcholine, Acetylcholinesterase, Alzheimer’s disease, Disintegrin ,Metalloproteinase, Aβ-derived diffusible ligands