Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of lamp-2-deficient mice.

Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of lamp-2-deficient mice. Am J Pathol. 2015 Jun;185(6):1713-23 Authors: Furuta A, Kikuchi H, Fujita H, Yamada D, Fujiwara Y, Kabuta T, Nishino I, Wada K, Uchiyama Y Abstract Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ultrastructural studies, we found various-shaped accumulations, including lipofuscin, glycolipid-like materials, and membranous structures, in the neurons and glial cells of Lamp-2-deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte lysosomes but were not observed in neurons. These pathological features indicate lysosomal storage disease; however, the findings are unlikely a consequence of deficiency of a single lysosomal enzyme. Although previous study results have shown a large amount of autophagic vacuoles in parenchymal cells of the vis...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research