title: Epigenetics: the neglected key to minimize learning and memory deficits in Down syndrome.
abstract: Down syndrome (DS) is the most common genetic intellectual disability, caused by the triplication of the human chromosome 21 (HSA21). Although this would theoretically lead to a 1.5 fold increase in gene transcription, transcript levels of many genes significantly deviate. Surprisingly, the underlying cause of this gene expression variation has been largely neglected so far. Epigenetic mechanisms, including DNA methylation and post-translational histone modifications, regulate gene expression and as such might play a crucial role in the development of the cognitive deficits in DS. Various overexpressed HSA21 proteins affect epigenetic mechanisms and DS individuals are thus likely to present epigenetic aberrations. Importantly, epigenetic marks are reversible, offering a huge therapeutic potential to alleviate or cure certain genetic deficits. Current epigenetic therapies are already used for cancer and epilepsy, and might provide novel possibilities for cognition-enhancing treatment in DS as well. To that end, this review discusses the still limited knowledge on epigenetics in DS and describes the potential of epigenetic therapies to reverse dysregulated gene expression.
authors.affiliation: Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: alaindekker@gmail.com.
authors.forename: Alain D
authors.initials: AD
authors.lastname: Dekker
authors.affiliation: Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Electronic address: p.p.de.deyn@umcg.nl.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: m.g.rots@umcg.nl.
authors.forename: Marianne G
authors.initials: MG
authors.lastname: Rots
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D004314:Down Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*
keywords: Alzheimer's disease; DNA methylation; Down syndrome; Epigenetic Editing; Epigenetics; Gene expression; Mental retardation; Post-translational histone modifications