title: Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of Down syndrome, autism, Fragile X and Rett syndrome.
abstract: 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.
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Council of Research, Bari, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Valenti
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Council of Research, Bari, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: de Bari
authors.affiliation: Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità Roma, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: De Filippis
authors.affiliation: INSERM U781 Hôpital Necker - Enfants Malades, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Henrion-Caude
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Council of Research, Bari, Italy. Electronic address: r.vacca@ibbe.cnr.it.
authors.forename: Rosa Anna
authors.initials: RA
authors.lastname: Vacca
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001321:Autistic Disorder / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005600:Fragile X Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects; D015518:Rett Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000975:Antioxidants
keywords: Autism; Down syndrome; Drug development; Epigallocatechine-3-gallate; Fragile X; Intellectual disability; Mitochondria; Mitochondrial dysfunction; Neurogenesis; Neuroplasticity; Oxidative phosphorylation; Oxidative stress; Rett syndrome