Ayush Chaurasia

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid‐ β (A β ) plaques and tau ( τ ) ‐related neurofibrillary tangles, often exacerbated by dysfunctional cellular clearance mechanisms. This manuscript explores the pivotal role of autophagy impairment in AD pathogenesis, with a specific focus on the AMPK/mTOR signaling axis as a primary regulatory pathway. Findings revealed that while mTOR overactivation suppresses autophagic flux and promotes the buildup of toxic protein aggregates, the activation of AMPK serves to restore homeostatic degradation processes. The review highlights that various pharmacological agent including rapamycin, metformin, trehalose, and curcumin, as well as repurposed drugs like lithium and statins can effectively enhance autophagy to ameliorate cognitive decline and neuroinflammation. Furthermore, herbal formulations such as Danggui Shaoyao San and phytoconstituents like Icariin demonstrate significant neuroprotective potential by modulating these same molecular pathways. Targeting autophagy represents a translationally viable approach for combating AD progression, with drug repurposing offering a time‐efficient and cost‐effective strategy. To advance these findings, future research should prioritize large‐scale clinical trials to validate the efficacy of autophagy‐inducing agents in human subjects. Additionally, investigating synergistic combinations of traditional bioactives with synthetic drugs and utilizing innovative delivery systems, such as intranasal nanotechnology‐based platforms to bypass the blood‐brain barrier, represents a promising frontier for developing effective, multi‐targeted treatments against AD.

Arsenic-induced neurotoxicity is increasingly recognized as a major global health issue, leading to both developmental and degenerative neurological impairments, therefore, arsenic is becoming one of the potent environmental neurotoxins that can lead to significant health risks, particularly through long-term exposure via water, food, and air. Arsenic exposure can initiate a range of pathological events such as-disruption of mitochondrial function, oxidative stress, apoptosis, and inflammatory processes, which result in neuronal damage and cognitive dysfunction. Conversely, neurotrophins growth factors that regulate neuronal survival, growth, and function, are emerging as promising neuroprotective agents against such neurotoxic effects. This article explores the neuroprotective roles of BDNF (Brain-derived neurotrophic factor) and NGF (Nerve growth factor) in counteracting arsenic-induced neurodegeneration, through the analysis of epidemiology and mechanism-based preclinical studies of last decade. Arsenic disrupts neurotrophin signaling by inhibiting Trk (Tropomyosin receptor kinase) receptor phosphorylation and downstream survival pathways PI3K-AKT (Phosphoinositide 3-kinase–Protein kinase B), ERK-CREB (Extracellular signal-regulated kinase-cAMP response element-binding protein), thus contributing to neurodegeneration. In animal models, BDNF supplementation exhibited reduction in oxidative stress by 45–60%, neuronal apoptosis declined by about 55%, and improvement in cognitive function up to 40%. Additionally, NGF supplementation shows a 40-55% reduction in apoptosis. By integrating toxicological mechanisms with therapeutic perspectives, this narrative review underscores the potential of neurotrophin-based strategies to mitigate arsenic-related neurodegeneration and highlights future research directions for translational applications.