Relationship of Lysosomal Storage Diseases (LSD) with Autophagy

Abstract

Lysosomes are organelles that break down damaged components or structures that have completed their task in the cell by the hydrolytic enzymes they contain and take part in the last step of the autophagic pathway. Autophagy, an evolutionarily conserved lysosomal pathway, is activated under stress conditions such as amino acid starvation, accumulation of unfolded proteins, or viral infection. The main task of autophagy is to remove damaged proteins, organelles and microorganisms that constitute the source of infection. During this degradation mechanism, autophagosomes are formed as a result of the interaction of lysosomes and autophagic vesicles carrying damaged proteins, and this formation is tightly controlled by cellular mechanisms. Damage during this interaction can disrupt cellular homeostasis and interfere with the survival of the organism. Lysosomal Storage Diseases (LDH) is one of the most common human genetic diseases that develop because of mutations on genes encoding lysosomal enzymes. To date, more than 70 LDHs have been identified. LDH is mainly caused by functional disorders of enzymes or lysosome-associated proteins in lysosomes. These disorders may cause undigested macromolecules to accumulate in the cells, compromising the proper functioning of the organs in which they are located. LDH can cause many systemic damages, especially in the nervous system, skeletal system, and reticuloendothelial system, especially in the early stages of the disease. Modulation and reactivation of autophagy is considered a new therapeutic approach for LDH. In this review, the general mechanisms of the relationship between lysosomal storage diseases and autophagy were evaluated together with treatment approaches.