Ovine ceroid lipofuscinosis (OCL6)

Postulated mechanism of neurodegeneration

R. D. Jolly, Steven U. Walkley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

It is proposed that ceroid lipofuscinosis in Southhampshire sheep (OCL(Southhampshire)) be also known as OCL6 as it is syntenic with CLN6 of humans. Histopathological studies show a severe and progressive neurodegeneration of the cerebral cortex which sometimes appears to have a laminar pattern and which is accompanied by a severe midcortical astrocytosis. Other studies have shown that fibroblasts maintained in tissue culture have abnormal regulation of ATP synthase. If this was reflected in neurons, then selective neuron death is likely to be the result of energy- linked excitotoxicity of neurons receiving abundant glutamate input. Increased sensitivity of the NMDA receptor due to inefficient repolarization of the neuron membrane would allow increased cellular uptake of calcium, increased formation of free radicals, and neuron death. The general hypothesis, as developed for other chronic neurodegenerative diseases, is partly based on application of various drugs that block or mediate parts of the pathway involved. The same approach could be used to help test the hypothesis in OCL6 lambs and if successful some of the drugs might have therapeutic potential. As patterns of neurodegeneration are similar in various other forms of ceroid lipofuscinosis accumulating subunit c of mitochondrial ATP synthase, the model may have more general application than merely to CLN6.

Original languageEnglish (US)
Pages (from-to)376-380
Number of pages5
JournalMolecular Genetics and Metabolism
Volume66
Issue number4
DOIs
StatePublished - Apr 1999
Externally publishedYes

Fingerprint

Ceroid
Neurons
Sheep
Mitochondrial Proton-Translocating ATPases
Neurodegenerative diseases
Tissue culture
Gliosis
Fibroblasts
N-Methyl-D-Aspartate Receptors
Neurodegenerative Diseases
Pharmaceutical Preparations
Cerebral Cortex
Free Radicals
Glutamic Acid
Chronic Disease
Adenosine Triphosphate
Calcium
Membranes

Keywords

  • ATP synthase
  • Ceroid lipofuscinosis
  • Excitotoxicity
  • Neurodegeneration

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Ovine ceroid lipofuscinosis (OCL6) : Postulated mechanism of neurodegeneration. / Jolly, R. D.; Walkley, Steven U.

In: Molecular Genetics and Metabolism, Vol. 66, No. 4, 04.1999, p. 376-380.

Research output: Contribution to journalArticle

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