Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

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17/09/2020
Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

International Journal of Molecular Sciences ,  May 2020
Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

Serena Stanga 1,2,3 , Anna Caretto 1,2 , Marina Boido 1,2,3 and Alessandro Vercelli 1,2,3

Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease.

However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the “mitochondrial switch” which occurs at the onset of neuronal degeneration.

We dissect the pathways related to mitochondrial dysfunctions which are shared among the most frequent or disabling neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. Can mitochondrial dysfunctions (affecting their morphology and activities) represent the early event eliciting the shift towards pathological neurobiological processes? Can mitochondria represent a common target against neurodegeneration? We also review here the drugs that target mitochondria in neurodegenerative diseases.

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Graphical_Abstract
Aging and environmental factors induce the ‘mitochondrial switch’ and, in turn, the transition to a pathological state due to their loss of function. Mitochondrial dysfunctions are the red thread in neurodegeneration since they unite different pathologies such as Alzheimer, Parkinson, Huntington diseases, Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy. Drugs targeting mitochondria could represent a new therapeutic approach able to cure different neurodegenerative disorders at the same time. 

1 Department of Neuroscience Rita Levi Montalcini, University of Turin, 10126 Turin, Italy
2 Neuroscience Institute Cavalieri Ottolenghi, University of Turin, 10043 Orbassano (TO), Italy
3 National Institute of Neuroscience (INN), 10125 Turin, Italy