Mitochondrial-Associated Metabolic Changes and Neurodegeneration in Huntington's Disease - from Clinical Features to the Bench

Huntington's disease (HD) is a genetic neurodegenerative disease selectively leading to striatal neurodegeneration, but also affecting the cortex and the hypothalamus. Although it is hard to predict the sequence of celldamaging events occurring in HD patients, several pathological mechanisms have been proposed to explain HD selective neurodegeneration and disease symptomatology. Abnormalities in mitochondrial function and bioenergetics contribute to cell death and have been reported in HD-affected individuals, both in central and peripheral tissues. Moreover, the latter has been characterized in several HD models. Thus, this review describes the converging mechanisms that lead to mitochondrial and metabolic abnormalities in thoroughly studied in vivo and in vitro HD models, including excitotoxicity, altered calcium handling, changes in mitochondrial structure and dynamics and transcription deregulation, which may represent important disease therapeutic targets. Furthermore, the review describes the current evidences of metabolic disturbances in the brain of HD-affected humans and of peripheral metabolic and mitochondrial changes, weight loss and endocrine abnormalities operating in the whole HD body.