title: Molecular pathologies of and enzyme replacement therapies for lysosomal diseases.
abstract: Lysosomal diseases comprise a group of inherited disorders resulting from defects of lysosomal enzymes and their cofactors, and in many of them the nervous system is affected. Recently, enzyme replacement therapy with recombinant lysosomal enzymes has been clinically available for several lysosomal diseases. Such enzyme replacement therapies can improve non-neurological disorders but is not effective for neurological ones. In this review, we discuss the molecular pathologies of lysosomal diseases from the protein structural aspect, current enzyme replacement therapies, and attempts to develop enzyme replacement therapies effective for lysosomal diseases associated with neurological disorders, i.e., production of enzymes, brain-specific delivery and incorporation of lysosomal enzymes into cells.
authors.affiliation: CREST, JST, Kawaguchi, Japan. sakuraba@rinshoken.or.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Fumiko
authors.initials: F
authors.lastname: Matsuzawa
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Aikawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Chiba
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Jigami
authors.forename: Kohji
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000818:Animals; D017077:Culture Media, Conditioned / Q000494:pharmacology; D057487:Enzyme Therapy; D004798:Enzymes / Q000737:chemistry / Q000235:genetics; D005678:G(M2) Ganglioside / Q000378:metabolism; D006801:Humans; D020140:Lysosomal Storage Diseases, Nervous System / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D008247:Lysosomes / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D012497:Sandhoff Disease / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D001619:beta-N-Acetylhexosaminidases / Q000737:chemistry / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D004798:Enzymes; D011993:Recombinant Fusion Proteins; D005678:G(M2) Ganglioside; D001619:beta-N-Acetylhexosaminidases