Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

Int J Mol Sci. 2020 May 25;21(10):3719. doi: 10.3390/ijms21103719.


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.

Keywords: cellular homeostasis; mitochondria; mitochondria biogenesis and dynamics; mitochondria targeting drugs; motor neuron diseases; neurodegeneration; neurodegenerative diseases; oxidative stress.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Amyotrophic Lateral Sclerosis / drug therapy
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Antioxidants / therapeutic use
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Muscular Atrophy, Spinal / drug therapy
  • Muscular Atrophy, Spinal / metabolism*
  • Neuroprotective Agents / therapeutic use
  • Organelle Biogenesis
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*


  • Antioxidants
  • Neuroprotective Agents