Pathobiology of Neuronal Storage Disease

The neuronal storage disorders are a complex family of diseases characterized by an abnormal accumulation of unmetabolized substances within neuronal somata. A wide variety of enzymatic and molecular events underlies this storage process and these are most often known to be associated with the lysosomal system of affected cells. The storage process is seen primarily as a lysosomal event, although for some types of storage diseases—for example, neuronal ceroid lipofuscinosis, this linkage is not firmly established. A complete discussion of the pathobiology of these diseases would necessarily encompass all pathogenetic events spanning from the molecular level to clinical manifestations of disease. This chapter discusses the consequences of these primary metabolic disturbances at the level of individual neurons or of functional groups of neurons. It is an attempt to develop a framework for understanding those factors making specific contributions to the malfunction of neurons and to the generation of those clinical manifestations that are characteristic of these diseases.