Send to

Choose Destination
Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:202-17. doi: 10.1016/j.neubiorev.2014.01.012. Epub 2014 Feb 15.

Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of Down syndrome, autism, Fragile X and Rett syndrome.

Author information

Institute of Biomembranes and Bioenergetics, National Council of Research, Bari, Italy.
Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità Roma, Italy.
INSERM U781 Hôpital Necker - Enfants Malades, Paris, France.
Institute of Biomembranes and Bioenergetics, National Council of Research, Bari, Italy. Electronic address:


Clinical manifestations typical of mitochondrial diseases are often present in various genetic syndromes associated with intellectual disability, a condition leading to deficit in cognitive functions and adaptive behaviors. Until now, the causative mechanism leading to intellectual disability is unknown and the progression of the condition is poorly understood. We first report latest advances on genetic and environmental regulation of mitochondrial function and its role in brain development. Starting from the structure, function and regulation of the oxidative phosphorylation apparatus, we review how mitochondrial biogenesis and dynamics play a central role in neurogenesis and neuroplasticity. We then discuss how dysfunctional mitochondria and alterations in reactive oxygen species homeostasis are potentially involved in the pathogenesis of various neurodevelopmental syndromes with a special focus on Down, Rett, Fragile X syndromes and autism spectrum disorders. Finally, we review and suggest novel therapeutic approaches aimed at improving intellectual disability by activating mitochondrial function and reducing oxidative stress to amiliorate the quality of life in the subjects affected.


Autism; Down syndrome; Drug development; Epigallocatechine-3-gallate; Fragile X; Intellectual disability; Mitochondria; Mitochondrial dysfunction; Neurogenesis; Neuroplasticity; Oxidative phosphorylation; Oxidative stress; Rett syndrome

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center