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REST, Ageing, and AD. By: Josh radparvar General Meeting 1 Spring 2014 14 April 2014. Outline. What is REST? What should happen? REST and AD Neuroprotective properties of REST Rest, cognitive preservation, and longevity Beyond AD. REST.
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REST, Ageing, and AD By: Josh radparvar General Meeting 1 Spring 2014 14 April 2014
Outline What is REST? What should happen? REST and AD Neuroprotective properties of REST Rest, cognitive preservation, and longevity Beyond AD
REST Repressor element 1-silencing transcription factor AKA neuron-restrictive silencer factor (NRSF) Represses genes that promote cell death and Alzheimer’s disease pathology
http://en.wikipedia.org/wiki/RE1-silencing_transcription_factorhttp://en.wikipedia.org/wiki/RE1-silencing_transcription_factor
Neuroprotective Properties Cell Viability Pro-Apoptotic Gene Expression
REST-deficient mice progressive age-related neurodegeneration REST is crucial for supporting viability in the ageing brain
REST and Tau • Braakstages: classification used to measure neurofibrillary tangles • Stages I and II are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain • Stages III and IV when there is also involvement of limbic regions such as the hippocampus • Stages V and VI when there is extensive neocortical involvement
REST and Cognitive Preservation • Nuclear REST levels in Prefrontal Cortex with neuropathological AD • Moderate/frequent plaques • Intermediate/high likelihood of AD by NIA-Regan criteria
REST and Longevity • Significance maintained even after multivariate adjustments for cognitive test scores and indices of neuropathology
“REST dysfunction may contribute to the pathogenesis of a number of different neurodegenerative disorders. In addition to AD, REST was also significantly depleted in frontotemporal dementia and dementia with Lewy bodies. In each of these disorders, REST was lost from the nucleus and appeared in autophagosomes…”
References Adopted from: Lu, T., et al. (2014). REST and stress resistance in ageing and Alzheimer/'s disease. Nature, 507(7493), 448-454. doi:10.1038/nature13163