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Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease)
journal contribution
posted on 2023-05-16, 16:18 authored by Jolly, RD, Brown, SC, Das, A, Walkley, SUThere 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. © 2002 Published by Elsevier Science Ltd.
History
Publication title
Neurochemistry InternationalVolume
40Issue
6Pagination
565-571ISSN
0197-0186Department/School
School of Health SciencesPublisher
Neurochemistry InternationalPlace of publication
AustraliaRepository Status
- Restricted