Autophagic and Lysosomal Disorders

Lysosomes are acid hydrolase–containing membrane-enclosed organelles that play a central role in autophagy or self-eating. As a result, aberrant lysosomal function and autophagy have been associated with multiple lysosomal storage and neurodegenerative disorders. While mutations in genes that are important for normal lysosomal function lead to lysosomal storage disorders like Batten disease, Gaucher’s disease, Tay–Sach’s disease, Krabbe disease, Niemann–Pick disease, etc., age- and neurodegenerative stimuli-influenced decrease in lysosomal clearance is associated to the pathogenesis of neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease (PD), Huntington’s disease. Recent studies have also identified an association between mutations of the glucocerebrosidase gene (for Gaucher’s disease) and PD. Considering the pathologies of these autophagic and lysosomal diseases, enhancement of lysosomal clearance machinery by gene therapy, enzyme replacement therapy, and stimulation of TFEB, the master regulator of lysosomal biogenesis has emerged as attractive therapeutic strategies for these disorders.