FIGURE 3.

Lysosomal dysfunction in neurodegeneration. Controlled degradation of proteins via lysosomal hydrolases is a key cellular homeostatic event. Aging, unknown factors, mutations in neurodegeneration-associated genes and in autophagy–lysosome genes, and the accumulation of cytosolic protein inclusions are negative regulators of lysosomal function. In a vicious circle, defective lysosomal function contributes to aging, accumulation of toxic gene products, and disease. Impaired lysosomal function may occur at the level of acidic hydrolase activity or by altered fusion and maturation of autophagy–lysosome organelles.