The "LEARn" (latent early-life associated regulation) model: an epigenetic pathway linking metabolic and cognitive disorders

Journal of Alzheimer's Disease : JAD
Debomoy K Lahiri, Bryan Maloney

Abstract

Diabetes, cardiovascular disease, hypertension, and other disorders have been unified within the metabolic syndrome. Recently, it has been proposed that Alzheimer's disease (AD) and other degenerative, age-related neurological disorders may also be etiologically linked to the metabolic syndrome in a metabolic-cognitive syndrome. We review current evidence in the field for this unification. In addition, we describe how the latent early-life associated regulation (LEARn) model provides specific mechanisms to predict genetic targets for both metabolic disorders, e.g., diabetes, and neurodegenerative disorders, e.g., AD. The LEARn model is based on environmental induction of latent epigenetic misregulation, which develops into disease upon suffering additional environmental insults. We review structural differences between gene sequences that are and are not susceptible to LEARn misregulation. In addition to suggesting research targets such as the IDE and SORCS1 genes, which are implicated in both AD and diabetes, LEARn suggests specific mechanisms for pre-disease remediation, based on nutritional adjustment of aberrant DNA methylation and oxidation. The possibility of a single metabolic-cognitive disorder opens up the possibility ...Continue Reading

Citations

Aug 8, 2014·International Journal of Geriatric Psychiatry·Karen A MatherPerminder S Sachdev
Mar 27, 2020·International Journal of Molecular Sciences·Olaia Martínez-IglesiasRamón Cacabelos
Jul 28, 2020·Environmental Science and Pollution Research International·Reyaz Hassan MirMubashir Hussain Masoodi

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