American Journal of Clinical Neurology and Neurosurgery
Articles Information
American Journal of Clinical Neurology and Neurosurgery, Vol.2, No.4, Jul. 2016, Pub. Date: Aug. 19, 2016
Neurogenetic Disorders of Down Syndrome and Potential Pharmacotherapies for Mental Retardation
Pages: 45-50 Views: 2679 Downloads: 2406
Authors
[01] Mohammed Rachidi, Molecular Genetics of Human Diseases, French Polynesia; University Paris 7 Denis Diderot, Paris, France.
Abstract
Background: Trisomy of human chromosome 21 is the most frequent genetic cause of mental retardation or intellectual disability and others phenotypes, including developmental defects, dysmorphic features and cognitive impairments collectively known as Down syndrome. Mainly a consequence of developmental and functional brain alterations, the mental retardation is the most invariable and invalidating neuropathological characteristic caused by the overdosage of genes triplicated in the chromosome 21. Methods and Results: The cytogenetic and molecular analysis facilitate the identification of the minimal region or Down Syndrome Chromosomal Region responsible for many phenotypes including mental retardation as the major constant phenotype caused by the overexpression of chromosome 21 genes. The complete sequence of human chromosome 21 and the transcriptome analysis in Down syndrome patients and in trisomic mouse models facilitate the genetic dissection of neurological and cognitive phenotypes. As a result of high degree of conservation of genomes and of molecular mechanisms between mouse and human, the mouse models of Down syndrome showed similar neuropathological features seen in Down syndrome persons and facilitate the identification of associated genetic targets. Conclusion: The genetic dissection of neurological phenotypes in trisomic mouse models highly developed our understanding of cellular and molecular mechanisms of gene overexpression caused by trisomy 21 and contributed significantly to the identification of specific genetic targets for pharmacological therapeutics. These pharmacological treatments in mouse models of Down syndrome allowed successfully post-drug rescue of neurological alterations and associated cognitive deficits and could be useful therapeutic tools of neurocognitive deficits and mental retardation seen in Down syndrome persons.
Keywords
Down Syndrome and Trisomy 21, Mental Retardation, Trisomic Mouse Models, Neurological Phenotypes, Learning and Memory, Molecular Targets, Genetic Pathways, Pharmacotherapies.
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