Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease)

R. D. Jolly, S. Brown, A. M. Das, Steven U. Walkley

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

There are at least eight genetic entities known as the ceroid-lipofuscinoses in humans which share clinical and pathological features that have caused them to be grouped together under the eponym of Batten disease. They present pathologically as lysosomal storage diseases but are also characterised by severe neurodegeneration. Although the biochemical defects appear primarily centred on lysosomes and defects in proteolysis, the link between this and pathogenesis of neuronal death is poorly understood. The pathogenesis of neurodegeneration has been studied particularly in two animal models these being the English setter dog and the New Zealand Southhampshire sheep (OCL6). In these, and some of the human entities, there is evidence of mitochondrial dysfunction. This includes the accumulation of subunit c of ATP synthase as a component of storage material in at least six of eight genetic forms of the disease; structural abnormalities of mitochondria and selective loss of neurons in areas of the brain that are particularly metabolically active. Direct evidence of dysfunction comes from mitochondrial function tests in fibroblasts and, in animal models, isolated liver mitochondria. Supporting evidence of mitochondrial dysfunction was shown by disturbances in proportions of energy-rich phosphates in fibroblasts in some of these diseases. If these various defects were reflected in neurons, then it would support the hypothesis that neuron death was associated with energy-linked excitotoxicity.

Original languageEnglish (US)
Pages (from-to)565-571
Number of pages7
JournalNeurochemistry International
Volume40
Issue number6
DOIs
StatePublished - 2002

Fingerprint

Neuronal Ceroid-Lipofuscinoses
Neurons
Animal Models
Fibroblasts
Eponyms
Ceroid
Lysosomal Storage Diseases
Inborn Genetic Diseases
Liver Mitochondrion
Lysosomes
New Zealand
Proteolysis
Sheep
Mitochondria
Adenosine Triphosphate
Phosphates
Dogs
Brain

Keywords

  • ATP synthase
  • Batten disease
  • Ceroid-lipofuscinosis
  • Excitotoxicity
  • Mitochondria
  • Subunit c

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease). / Jolly, R. D.; Brown, S.; Das, A. M.; Walkley, Steven U.

In: Neurochemistry International, Vol. 40, No. 6, 2002, p. 565-571.

Research output: Contribution to journalArticle

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