Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 1:445:190-206.
doi: 10.1016/j.neuroscience.2020.04.037. Epub 2020 Apr 29.

Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders

Michela Fagiolini  1 , Annarita Patrizi  2 , Jocelyn LeBlanc  2 , Lee-Way Jin  3 , Izumi Maezawa  3 , Sarah Sinnett  4 , Steven J Gray  4 , Sophie Molholm  5 , John J Foxe  6 , Michael V Johnston  7 , Sakkubai Naidu  7 , Mary Blue  7 , Ahamed Hossain  7 , Shilpa Kadam  7 , Xinyu Zhao  8 , Quiang Chang  8 , Zhaolan Zhou  9 , Huda Zoghbi  10
Affiliations
Review

Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders

Michela Fagiolini et al. Neuroscience. .

Abstract

Disruptions in the gene encoding methyl-CpG binding protein 2 (MECP2) underlie complex neurodevelopmental disorders including Rett Syndrome (RTT), MECP2 duplication disorder, intellectual disabilities, and autism. Significant progress has been made on the molecular and cellular basis of MECP2-related disorders providing a new framework for understanding how altered epigenetic landscape can derail the formation and refinement of neuronal circuits in early postnatal life and proper neurological function. This review will summarize selected major findings from the past years and particularly highlight the integrated and multidisciplinary work done at eight NIH-funded Intellectual and Developmental Disabilities Research Centers (IDDRC) across the US. Finally, we will outline a path forward with identification of reliable biomarkers and outcome measures, longitudinal preclinical and clinical studies, reproducibility of results across centers as a synergistic effort to decode and treat the pathogenesis of the complex MeCP2 disorders.

Keywords: animal models; biomarkers; neurodevelopmental disorders; signaling pathways; translational.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aldehri MTY, Alnaami I, Jahanshahi A, Hescham S (2018) Deep brain stimulation for Alzheimer’s Disease: an update. Surg Neurol Int 9:58. - PMC - PubMed
    1. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23:185–188. - PubMed
    1. Artoni P, Piffer A, Vinci V, LeBlanc J, Nelson CA, Hensch TK, Fagiolini M (2019) Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients. Proc Natl Acad Sci U S A:22. - PMC - PubMed
    1. Asaka Y, Juglott DG, Zhang L, Eubanks JH, Fitzsimonds RM (2006) Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis 21:217–227. - PubMed
    1. Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY (2013) An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell 152:984–996. - PMC - PubMed

Publication types