Down syndrome: Neurobiological alterations and therapeutic targets

Rosa Anna Vacca; Sweta Bawari; Daniela Valenti; Devesh Tewari; Seyed Fazel Nabavi; Samira Shirooie; Archana N Sah; Mariateresa Volpicella; Nady Braidy; Seyed Mohammad Nabavi

doi:10.1016/j.neubiorev.2019.01.001

Down syndrome: Neurobiological alterations and therapeutic targets

Neurosci Biobehav Rev. 2019 Mar:98:234-255. doi: 10.1016/j.neubiorev.2019.01.001. Epub 2019 Jan 4.

Authors

Affiliations

¹ Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy. Electronic address: r.vacca@ibiom.cnr.it.
² Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun University, Nainital, India.
³ Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy.
⁴ Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Health Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
⁵ Department of Pharmacology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
⁶ Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
⁷ Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Australia.
⁸ Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

PMID: 30615933
DOI: 10.1016/j.neubiorev.2019.01.001

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.

Keywords: Chromosome 21 trisomy; Mitochondrial dysfunction; Neurodegeneration; Neurodevelopment disease; Neurogenesis; Neurotransmission.

Publication types

Review

MeSH terms

Aneuploidy
Animals
Disease Models, Animal
Down Syndrome / physiopathology*
Down Syndrome / therapy
Humans
Intellectual Disability / physiopathology*
Learning / physiology*
Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

Receptors, N-Methyl-D-Aspartate