Pathogenic mechanisms in lysosomal disease: A reappraisal of the role of the lysosome

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32 Citations (Scopus)

Abstract

The view that lysosomes simply represent end organelles in the serial degradation of polymeric molecules derived from the cell surface and its interior has led to major misconceptions about the nature of lysosomal storage diseases and the pathogenic cascades that characterize them. Accordingly, lysosomal storage bodies are often considered 'inert', inducing cell dysfunction and death primarily through mechanical overcrowding of normal organelles or by other non-specific means leading to generalized cytotoxicity. However, modern studies of lysosomes and their component proteins provide evidence to support a far greater role for these organelles in cell metabolism. In intimate association with endosomal, autophagosomal and related vesicular systems, the greater lysosomal system can be conceptualized as a vital recycling centre that serves as a central metabolic coordinator, influencing literally every aspect of the cell, from signal transduction to regulation of gene expression. Conclusion: This broader view of the role of lysosomes in cells not only provides insight into how single gene defects impacting on lysosomal function can result in the plethora of complex cellular transformations characteristic of these diseases, but also suggests new and innovative therapies that may hold considerable promise for ameliorating disease progression.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalActa Paediatrica, International Journal of Paediatrics
Volume96
Issue numberSUPPL. 455
DOIs
StatePublished - Apr 2007

Fingerprint

Lysosomes
Organelles
Lysosomal Storage Diseases
Investigational Therapies
Inborn Genetic Diseases
Gene Expression Regulation
Recycling
Disease Progression
Signal Transduction
Cell Death
Proteins

Keywords

  • Autophagosome
  • Axonal spheroid
  • Cholesterol
  • Endosome
  • Ganglioside
  • Glycosaminoglycan
  • Glycosphingolipid
  • Lysosome
  • Proteoglycans
  • Raft
  • Retrosome
  • Sphingomyelin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

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abstract = "The view that lysosomes simply represent end organelles in the serial degradation of polymeric molecules derived from the cell surface and its interior has led to major misconceptions about the nature of lysosomal storage diseases and the pathogenic cascades that characterize them. Accordingly, lysosomal storage bodies are often considered 'inert', inducing cell dysfunction and death primarily through mechanical overcrowding of normal organelles or by other non-specific means leading to generalized cytotoxicity. However, modern studies of lysosomes and their component proteins provide evidence to support a far greater role for these organelles in cell metabolism. In intimate association with endosomal, autophagosomal and related vesicular systems, the greater lysosomal system can be conceptualized as a vital recycling centre that serves as a central metabolic coordinator, influencing literally every aspect of the cell, from signal transduction to regulation of gene expression. Conclusion: This broader view of the role of lysosomes in cells not only provides insight into how single gene defects impacting on lysosomal function can result in the plethora of complex cellular transformations characteristic of these diseases, but also suggests new and innovative therapies that may hold considerable promise for ameliorating disease progression.",
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