The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases.

Abstract:

:Neurobiological disorders have diverse manifestations and symptomology. Neurodegenerative disorders, such as Alzheimer's disease, manifest late in life and are characterized by, among other symptoms, progressive loss of synaptic markers. Developmental disorders, such as autism spectrum, appear in childhood. Neuropsychiatric and affective disorders, such as schizophrenia and major depressive disorder, respectively, have broad ranges of age of onset and symptoms. However, all share uncertain etiologies, with opaque relationships between genes and environment. We propose a 'Latent Early-life Associated Regulation' (LEARn) model, positing latent changes in expression of specific genes initially primed at the developmental stage of life. In this model, environmental agents epigenetically disturb gene regulation in a long-term manner, beginning at early developmental stages, but these perturbations might not have pathological results until significantly later in life. The LEARn model operates through the regulatory region (promoter) of the gene, specifically through changes in methylation and oxidation status within the promoter of specific genes. The LEARn model combines genetic and environmental risk factors in an epigenetic pathway to explain the etiology of the most common, that is, sporadic, forms of neurobiological disorders.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Lahiri DK,Maloney B,Zawia NH

doi

10.1038/mp.2009.82

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

992-1003

issue

11

eissn

1359-4184

issn

1476-5578

pii

mp200982

journal_volume

14

pub_type

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