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Title:
Lysosomal diseases; Basic pathology and treatment strategy

Norio Sakai
Department of Pediatrics
Osaka University Graduate School of Medicine

Abstract:
 Lysosomal diseases are one of the most common disease group of inborn error of metabolic diseases. Lysosome was recognized as dust box in the cell, however recently it is known to be involved in global reproduction system via autophagy and mitophagy. And it is recognized as key organelle in cellular function.
  This group of diseases is always at frontier in the phase of molecular cloning and development of molecular treatment. I would summarize the elucidation of molecular pathology for lysosomal diseases including my laboratory contribution. Main presentation is focused on Krabbe disease (globoid-cell leukodystrophy) that is characterized as metabolic demyelination disease and mucolipidosis that has unique characteristics because most of lysosomeal enzymes are luck in the lysosome showing overlapping phenotype of lysosomal diseases.
  I would try to mention about the treatment strategy and future development including gene therapy and chaperone treatment.

References
1) Sakai, N., Inui, K., Fujii, N., Fukushima, H., Nishimoto, J., Yanagihara, I., Isegawa, Y., Iwamatsu, A. and Okada, S. Krabbe disease: Isolation and characterization of a full-length cDNA for human galactocerebrosidase. Biochem Biophys Res Commun, 198:485-491, 1994
2) Sakai N., Pathogenesis of leukodystrophy for Krabbe disease: molecular mechanism and clinical treatment. Brain Dev, 31(7):485-7, 2009
3) Hossain MA, Otomo T, Saito S, Ohno K, Sakuraba H, Hamada Y, Ozono K, Sakai N., Late-onset Krabbe disease is predominant in Japan and its mutant precursor protein undergoes more effective processing than the infantile-onset form. Gene, 534(2):144-54, 2014
4) Otomo T, Muramatsu T, Yorifuji T, Okuyama T, Nakabayashi H, Fukao T, Ohura T, Yoshino M, Tanaka A, Okamoto N, Inui K, Ozono K, Sakai N, Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype phenotype correlation. J Hum Genet, 54(3):145-51, 2009
5) Otomo T, Higaki K, Nanba E, Ozono K, Sakai N., Inhibition of autophagosome formation restores mitochondrial function in mucolipidosis II and III skin fibroblasts. Mol Genet Metab, 98(4):393-9, 2009
6) Otomo T, Higaki K, Nanba E, Ozono K, Sakai N., Lysosomal storage causes cellular dysfunction In mucolipidosis II skin fibroblasts. J Biol Chem, 286(40): 35283-90, 2011
7) Otomo T, Hossain MA, Ozono K, Sakai N., Genistein reduces heparan sulfate accumulation in human mucolipidosis II skin fibroblasts. Mol Genet Metab, 105(2):266-9, 2012