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A range of disorders have been recognized: varying from psychomotor retardation in childhood, to intermittent neuropsychiatric disease with ataxia and other motor disabilities, such as Friedreich's and other spinocerebellar ataxias [70], as well as neural diseases where mental deficits are also visible such as Parkinson's disease, and Alzheimer's disease (AD) [70]In Parkinsons Disease which has been deeply investigated, KGDHC Activity is reduced, coupled to elevated levels of monoamine oxidase B [71] and cytosolic accumulation of cytochrome c which inturn activates other pathways, including cell death cascades and enzyme inhibition which alters Ca2+homeostasis [72] The KGDHC enzyme is further a target for ubiquitination-dependent degradation in mitochondria by binding of Siah2, the RING finger ubiquitin-protein isopeptide ligase 2, encoded by gene siah2 [73]

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21, May 2019, pp