Molecular pathologies of and enzyme replacement therapies for lysosomal diseases

CNS Neurol Disord Drug Targets. 2006 Aug;5(4):401-13. doi: 10.2174/187152706777950738.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Culture Media, Conditioned / pharmacology
  • Enzyme Therapy*
  • Enzymes / chemistry
  • Enzymes / genetics
  • G(M2) Ganglioside / metabolism
  • Humans
  • Lysosomal Storage Diseases, Nervous System / enzymology*
  • Lysosomal Storage Diseases, Nervous System / genetics
  • Lysosomal Storage Diseases, Nervous System / therapy
  • Lysosomes / enzymology*
  • Lysosomes / genetics
  • Lysosomes / pathology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / therapeutic use*
  • Sandhoff Disease / enzymology
  • Sandhoff Disease / genetics
  • Sandhoff Disease / physiopathology
  • Tay-Sachs Disease / enzymology
  • Tay-Sachs Disease / genetics
  • Tay-Sachs Disease / physiopathology
  • beta-N-Acetylhexosaminidases / chemistry
  • beta-N-Acetylhexosaminidases / genetics


  • Culture Media, Conditioned
  • Enzymes
  • Recombinant Fusion Proteins
  • G(M2) Ganglioside
  • beta-N-Acetylhexosaminidases