Cellular pathology of lysosomal storage disorders

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Lysosomal storage disorders are rare, inborn errors of metabolism characterized by intralysosoreal accumulation of unmetabolized compounds. The brain is commonly a central focus of the disease process and children and animals affected by these disorders often exhibit progressively severe neurological abnormalities. Although most storage diseases result from loss of activity of a single enzyme responsible for a single catabolic step in a single organelle, the lysosome, the overall features of the resulting disease belies this simple beginning. These are enormously complex disorders with metabolic and functional consequences that go far beyond the lysosome and impact both soma-dendritic and axonal domains of neurons in highly neuron type-specific ways. Cellular pathological changes include growth of ectopic dendrites and new synaptic connections and formation of enlargements in axons far distant from the lysosomal defect. Other storage diseases exhibit neuron death, also occurring in a cell-selective manner. The functional links between known molecular genetic and enzyme defects and changes in neuronal integrity remain largely unknown. Future studies on the biology of lysosomal storage diseases affecting the brain can be anticipated to provide insights not only into these pathogenic mechanisms, but also into the role of lysosomes and related organelles in normal neuron function.

Original languageEnglish (US)
Pages (from-to)175-193
Number of pages19
JournalBrain Pathology
Volume8
Issue number1
StatePublished - 1998

Fingerprint

Lysosomes
Pathology
Neurons
Organelles
Lysosomal Storage Diseases
Inborn Errors Metabolism
Brain
Carisoprodol
Enzymes
Dendrites
Axons
Molecular Biology
Growth

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine

Cite this

Cellular pathology of lysosomal storage disorders. / Walkley, Steven U.

In: Brain Pathology, Vol. 8, No. 1, 1998, p. 175-193.

Research output: Contribution to journalArticle

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