| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Furuta, Akiko Kikuchi, Hisae Fujita, Hiromi Yamada, Daisuke Fujiwara, Yuuki Kabuta, Tomohiro Nishino, Ichizo Wada, Keiji Uchiyama, Yasuo |
| Description |
Author Affiliation: Furuta A ( Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: afuruta@juntendo.ac.jp.); Kikuchi H ( Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.); Fujita H ( Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.); Yamada D ( Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.); Fujiwara Y ( Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan); Kabuta T ( Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.); Nishino I ( Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.); Wada K ( Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.); Uchiyama Y ( Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.) |
| 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 visceral organs, these findings were rarely detected in the brain tissue except for some axons in the substantia nigra, in which abundant activated microglial cells with increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous system has a possible role in the degradation of the various macromolecules in lysosomes and an additional function concerning protection from oxidative stress, especially in the substantia nigra. |
| File Format |
HTM / HTML |
| ISSN |
00029440 |
| Issue Number |
6 |
| Volume Number |
185 |
| e-ISSN |
15252191 |
| Journal |
The American Journal of Pathology |
| Language |
English |
| Publisher |
Elsevier (on behalf of the American Society for Investigative Pathology) |
| Publisher Date |
2015-06-01 |
| Publisher Place |
United States |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Research Support, Non-u.s. Gov't Mesencephalon Neurons Glycogen Lysosomes Male Discipline Pathology Metabolism Journal Article Mice, Knockout Pathology Animals Lysosomal Storage Diseases Genetics Lysosomal-associated Membrane Protein 2 Mice Disease Models, Animal |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Pathology and Forensic Medicine |
