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Cited by 229Genetics and Neurodevelopmental DisordersEpigenetics and DNA MethylationAutism Spectrum Disorder Research

The DOI matches its Crossref record; 1,085 of the 1,085 references it cites were found in a registry or an index.

An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy

Millan, Mark J.·2013·Neuropharmacology
DOI 10.1016/j.neuropharm.2012.11.015
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Abstract

Neurodevelopmental disorders (NDDs) are characterized by aberrant and delayed early-life development of the brain, leading to deficits in language, cognition, motor behaviour and other functional domains, often accompanied by somatic symptoms. Environmental factors like perinatal infection, malnutrition and trauma can increase the risk of the heterogeneous, multifactorial and polygenic disorders, autism and schizophrenia. Conversely, discrete genetic anomalies are involved in Down, Rett and Fragile X syndromes, tuberous sclerosis and neurofibromatosis, the less familiar Phelan-McDermid, Sotos, Kleefstra, Coffin-Lowry and "ATRX" syndromes, and the disorders of imprinting, Angelman and Prader-Willi syndromes. NDDs have been termed "synaptopathies" in reference to structural and functional disturbance of synaptic plasticity, several involve abnormal Ras-Kinase signalling ("rasopathies"), and many are characterized by disrupted cerebral connectivity and an imbalance between excitatory and inhibitory transmission. However, at a different level of integration, NDDs are accompanied by aberrant "epigenetic" regulation of processes critical for normal and orderly development of the brain. Epigenetics refers to potentially-heritable (by mitosis and/or meiosis) mechanisms controlling gene expression without changes in DNA sequence. In certain NDDs, prototypical epigenetic processes of DNA methylation and covalent histone marking are impacted. Conversely, others involve anomalies in chromatin-modelling, mRNA splicing/editing, mRNA translation, ribosome biogenesis and/or the regulatory actions of small nucleolar RNAs and micro-RNAs. Since epigenetic mechanisms are modifiable, this raises the hope of novel therapy, though questions remain concerning efficacy and safety. The above issues are critically surveyed in this review, which advocates a broad-based epigenetic framework for understanding and ultimately treating a diverse assemblage of NDDs ("epigenopathies") lying at the interface of genetic, developmental and environmental processes. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.

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  1. Gadalla, K.K., Bailey, M.E., Spike, R.C., Ross, P.D., Woodard, K.T., Kalburgi, S.N., Bachaboina, L., Deng, J.V., West, A.F., Samulski, R.J., Gray, S.J., Cobb, S.R. Improved survival and reduced phenotypic severity following AAV9 MECP2 gene transfer to neonatal and juvenile male MeCP2 knockout mice. Mol. Ther., in press.
  2. Glausier, J.R., Lewis, D.A. Dendritic spine pathology in schizophrenia. Neuroscience, in press.
  3. Gray, S.J. Gene therapy and neurodevelopmental disorders. Neuropharmacology, in press.
  4. Malina, A., Mills, J.R., Pelletier, J. Emerging therapeutics targeting mRNA translation. Hot Summer Airport Retrosp. Biol., in press.
  5. Relkovic, D., Isles, A.R. Behavioural and cognitive profiles of mouse models for Prader–Willi syndrome. Brain Res. Bull., in press.
  6. Shulha, 2011, Epigenetic signatures of autism, Arch. Gen. Psychiatry, 7, E1
  7. Uchino, S., Waga, C. Shank3 as an autism spectrum disorder-associated gene. Brain Dev., in press.
  8. Waddington, 1942, The epigenotype, Endeavour, 1, 18
  9. Weiss, 2005, The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1, Curr. Biol., 15, 1961, 10.1016/j.cub.2005.09.043 · DOI

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Metadata

Authors
Millan, M. J.
Corresponding author
Millan, Mark J.
ORCID
Millan, Mark J.
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2013-05
Volume
68
Pages
2-82
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2012.11.015
OpenAlex
W2028188824
Cited by
229
References
1,085
Citations by year
2026: 6 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 14 · 2021: 12 · 2020: 10 · 2019: 27 · 2018: 18 · 2017: 17 · 2016: 30 · 2015: 17 · 2014: 34 · 2013: 20
FWCI
2.84
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
neurodevelopmental disorders, epigenetics, DNA methylation, histone modifications, chromatin regulation, mRNA splicing, microRNA, small nucleolar RNA, ribosome biogenesis, synaptic plasticity, synaptopathy, RASopathies, excitatory-inhibitory imbalance, autism spectrum disorder, schizophrenia, Down syndrome, Rett syndrome, fragile X syndrome, tuberous sclerosis complex, neurofibromatosis, Phelan-McDermid syndrome, Sotos syndrome, Kleefstra syndrome, Coffin-Lowry syndrome, Angelman syndrome, Prader-Willi syndrome, imprinting disorders, epigenetic therapy
MeSH terms
Autistic Disorder, Central Nervous System Diseases, Humans, Schizophrenia, DNA Methylation, RNA, Untranslated, Epigenesis, Genetic

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