The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders

AbstractNeurological disorders (NDs) are characterized by progressive neuronal dysfunction leading to synaptic failure, cognitive impairment, and motor injury. Among these diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington ’s disease (HD), and amyotrophic lateral sclerosis (ALS) have raised a significant research interest. These disorders present common neuropathological signs, including neuronal dysfunction, protein accumulation, oxidative damage, and mitochondrial abnormalities. In this context, mitochondrial impa irment is characterized by a deficiency in ATP production, excessive production of reactive oxygen species, calcium dysregulation, mitochondrial transport failure, and mitochondrial dynamics deficiencies. These defects in mitochondrial health could compromise the synaptic process, leading to early c ognitive dysfunction observed in these NDs. Interestingly, skin fibroblasts from AD, PD, HD, and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these NDs. In this context, fibroblasts are considered a viable model for studying neu rodegenerative changes due to their metabolic and biochemical relationships with neurons. Also, studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD, PD, HD, and ALS. Interestingly, these mit ochondrial abnormalities have been observed in the ...
Source: Translational Neurodegeneration - Category: Neurology Source Type: research