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Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs)

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An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy.

Mark J Millan¹

¹Unit for Research and Discovery in Neuroscience, IDR Servier, 125 chemin de ronde, 78290 Croissy sur Seine, Paris, France. mark.millan@fr.netgrs.com

Neuropharmacology

|December 19, 2012

Summary

Neurodevelopmental disorders (NDDs) involve brain development issues, impacting cognition and behavior. This review proposes an epigenetic framework, "epigenopathies," to understand and treat these complex conditions.

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Area of Science:

Neuroscience
Genetics
Developmental Biology
Epigenetics

Background:

Neurodevelopmental disorders (NDDs) manifest as delayed brain development, causing deficits in language, cognition, motor skills, and behavior.
NDDs are multifactorial, influenced by genetic anomalies (e.g., Down syndrome, autism) and environmental factors (e.g., infection, malnutrition).
These disorders are linked to synaptic dysfunction ('synaptopathies'), aberrant Ras-Kinase signaling ('rasopathies'), and disrupted brain connectivity.

Purpose of the Study:

To critically survey the role of epigenetic dysregulation in the pathogenesis of NDDs.
To advocate for a broad-based epigenetic framework for understanding and treating NDDs.
To explore the potential for novel therapies targeting modifiable epigenetic mechanisms.

Main Methods:

Review of existing literature on the genetic, environmental, and epigenetic underpinnings of NDDs.
Analysis of how epigenetic processes like DNA methylation, histone modification, and chromatin remodeling are impacted in NDDs.
Examination of non-coding RNA and translational control mechanisms in neurodevelopmental contexts.

Main Results:

NDDs are characterized by aberrant epigenetic regulation affecting gene expression without altering DNA sequence.
Specific epigenetic mechanisms implicated include DNA methylation, histone marking, chromatin remodeling, and mRNA processing.
Disruptions in ribosome biogenesis and regulatory RNAs (miRNAs, snoRNAs) also contribute to NDDs.

Conclusions:

Epigenetic dysregulation is a central feature of many NDDs, termed 'epigenopathies'.
The modifiable nature of epigenetic mechanisms offers promising therapeutic avenues.
An integrated epigenetic framework is crucial for advancing the understanding and treatment of NDDs.