Therapeutics immunotargets for Tauopathy.

Abstract

Alzheimer's disease is a multi-factor involved neurodegenerative disease. In Alzheimer's condition, the pathological protein transfer from cell to cell and cause other cells to degenerate, similar to prion like diseases, this pathological protein transfer is exacerbated by neuroinflammation, mitochondrial dysfunction, oxidative stress, autophagy impairment, and cholinergic deficits. Neuroinflammation, driven by chronic microglial activation, produces excessive cytokines that worsen Tau hyperphosphorylation. Mitochondrial dysfunction, characterized by impaired energy metabolism, enzyme deficits in the TCA cycle, and ROS overproduction, leads to oxidative damage to proteins, lipids, and nucleic acids. Oxidative stress further accelerates neuronal damage. Autophagy dysfunction, caused by impaired mTOR signalling, disrupts the clearance of Aβ and Tau, facilitating their accumulation. Additionally, cholinergic deficits, including reduced acetylcholine levels, impair cognitive functions like memory and learning. Therapeutic approaches targeting these interconnected mechanisms, such as modulating inflammation, restoring mitochondrial and autophagy functions, and addressing the amyloid and Tau pathways will offers promising directions for treating Alzheimer's disease by developing an effective intervention to manage this debilitating disorder.