Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders

Abstract

Heavy metals such as lead, mercury, cadmium, magnesium, manganese, arsenic, copper pose considerable threats to neuronal health and are increasingly recognized as factors contributing to aging-related neurodegeneration. Exposure to these environmental toxins disrupts cellular homeostasis, resulting in oxidative stress and compromising critical cellular processes, particularly the autophagy-lysosomal pathway. This pathway is vital for preserving cellular integrity by breaking down damaged proteins and organelles; however, toxicity from heavy metals can hinder this function, leading to the buildup of harmful substances, inflammation, and increased neuronal injury. As individuals age, the consequences of neurodegeneration become more significant, raising the likelihood of developing disorders like Alzheimer’s and Parkinson’s disease. This review explores the intricate relationship between heavy metal exposure, dysfunction of the autophagy-lysosomal pathway, and aging-related neurodegeneration, emphasizing the urgent need for a comprehensive understanding of these mechanisms. The insights gained from this analysis are crucial for creating targeted therapeutic approaches aimed at alleviating the harmful effects of heavy metals on neuronal health and improving cellular resilience in aging populations.