Roles of long noncoding RNAs in brain development, functional

diversification and neurodegenerative diseases.

• Their involvement in the fundamental cellular processes including

regulate gene expression at epigenetics, transcription, and post-
transcription highlighted a central role in cell homeostasis

• lncRNAs play important roles in brain development, neuron function

and maintenance, and neurodegenerative diseases

• several of these contain lncRNAs genomic binding sites for the

transcriptional repressor REST

• many of these lncRNAs result in altered epigenetic gene regulation in

diseased neurons, and that contributes to neurodegeneration
 Paradigms for how long ncRNAs function.

(inhibiting RNA polymerase II recruitment)

upstream
noncoding
promoter

miRNAs, piRNAs (Piwi-ARNs)

RNA–protein complex

Wilusz J E et al. Genes Dev. 2009;23:1494-1504

Copyright © 2009 by Cold Spring Harbor Laboratory Press

New scientific research in the Alzheirmer´s disease

REST and stress resistance in ageing and Alzheimer’s disease

Nature 507, 448–454 (27 March 2014)

• Repressor element 1-silencing transcription factor (REST; also known

as neuron-restrictive silencer factor, NRSF)

• REST represses genes that promote cell death and Alzheimer’s

disease pathology
• REST induces the expression of stress response genes
• REST potently protects neurons from oxidative stress and amyloid β-
protein toxicity, and conditional deletion of REST in the mouse brain leads
to age-related neurodegeneration.