The lysosomal system: Pathology

Lysosomal storage diseases (LSDs) represent a group of over 70 monogenic diseases that are generally defined by lysosomal system dysfunction. The central nervous system (CNS) is frequently affected, with more than two-thirds of all LSDs exhibiting extensive neurological impairment. The progressive clinical and pathological course of LSDs highlights the indispensable role of the lysosome, especially in the CNS, which is particularly vulnerable. Autophagy is a critical homeostatic mechanism that is constitutively active and also selective for targeting intracellular components, including proteins and organelles for lysosomal degradation. Calcium plays a critical role as a second messenger involved in a wide range of cellular functions and signaling cascades. The first and most logical is simply a degenerative change that impacts the length of dendrites as well as the number of dendritic spines as lysosomal pathology compromises cell function.