Electron Transport Disturbances and Neurodegeneration: From Albert Szent-Györgyi’s Concept (Szeged) till Novel Approaches to Boost Mitochondrial Bioenergetics

Figure 5

The involvement of mitochondrial dysfunction in Huntington’s disease. Complex II deficiency, the predominant electron transport disorder in HD has long been linked to the deleterious effects of mutant huntingtin aggregation, a pathognomonic alteration in HD, and inhibitors of complex II (such as 3-nitropropionic acid (3-NP) and malonate) are used in experimental modeling of the disease. Disturbed OXPHOS in the affected cells can lead to the development of a vicious circle, eventually leading to cell death. Novel findings link PGC-1α dysfunction to the pathogenesis of HD at multiple levels, the restoration of which may hold therapeutic value. (↑ = increased presence/expression/activity; ↓ = decreased presence/expression/activity; arrow = promotion; bulb-headed arrow = inhibition/deterioration.)