Down syndrome: Neurobiological alterations and therapeutic targets. (March 2019)

• Record Type: Journal Article
• Authors: Vacca, Rosa Anna; Bawari, Sweta; Valenti, Daniela; Tewari, Devesh; Nabavi, Seyed Fazel; Shirooie, Samira; Sah, Archana N.; Volpicella, Mariateresa; Braidy, Nady; Nabavi, Seyed Mohammad
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 98(2019)
• Page Start: 234
• Page End: 255
• Publication Date: 2019-03
• Subjects: Aβ beta-amyloid -- AD Alzheimer's disease -- AMPK 5′ AMP-activated protein kinase -- APP amyloid precursor protein -- BAX BCL2-Associated X Protein -- CAT catalase -- CBS cystathionine beta-synthase -- CNS central nervous system -- CoQ10 Coenzyme Q10 -- Drp1 dynamin-related protein 1 -- DS Down syndrome -- DSCR Down syndrome critical region -- DYRK1A dual-specificity tyrosine (Y)-phosphorylation regulated kinase 1A -- EGCG epigallocatechin-3-gallate -- GABA γ-aminobutyric acid -- GIs γ-secretase inhibitors -- GPCR G-protein coupled receptor -- GPX glutathione peroxidase -- Hsa21 human chromosome 21 -- iPSCs induced pluripotent stem cells -- LTD long-term depression -- LTP long-term potentiation -- Mecp2 methyl-CpG binding protein 2 -- miRNAs microRNAs -- Mnf2 mitofusin 2 -- MRC mitochondrial respiratory chain -- mTOR mammalian target of rapamycin -- NAM negative allosteric modulator -- NFAT nuclear factor of activated T-cells -- NKCC1 Na-K-clcotransporter 1 -- NMDA N-methyl-d- aspartate -- NPCs neural progenitor cells -- NRIP1 nuclear receptor interacting protein 1 -- Opa1 optic atrophy 1 -- PKA protein kinase -- APiB C-labeled Pittsburgh compound B -- RCAN1 regulator of calcineurin 1 -- RIP140 receptor-interacting protein 140 -- ROS reactive oxygen species -- SOD superoxide dismutase -- TSP-1 thrombospondin 1; Chromosome 21 trisomy -- Neurodevelopment disease -- Neurotransmission -- Neurogenesis -- Mitochondrial dysfunction -- Neurodegeneration; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2019.01.001
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Down syndrome is both a neurodevelopment and neurodegenerative disorder. Genetic and metabolic alterations involved in Down syndrome neuropathology are discussed. Drugs targeting altered genes and metabolic pathways for therapeutic challenge in DS are discussed. Abstract: Down syndrome (DS) is a genetic disease that occurs due to an aneuploidy of human chromosome 21. Trisomy of chromosome 21 is a primary genetic cause of developmental abnormalities leading to cognitive and learning deficits. Impairments in GABAergic transmission, noradrenergic neuronal loss, anomalous glutamatergic transmission and N -methyl-d -aspartate receptor signalling, mitochondrial dysfunction, increased oxidative stress and inflammation, differentially expressed microRNAs, increased expression of crucial chromosome 21 genes, and DNA hyper-methylation and hyperactive homocysteine trans-sulfuration pathway, are common incongruities that have been reported in DS and might contribute to cognitive impairment and intellectual disability. This review provides an update on metabolic and neurobiological alterations in DS. It also provides an overview of the currently available pharmacological therapies that may influence and/or reverse these alterations in DS.