REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons.

During aging, brain performances decline. Cellular senescence is one of the aging drivers and a key feature of a variety of human age-related disorders. The transcriptional repressor RE1-silencing transcription factor (REST) has been associated with aging and higher risk of neurodegenerative disorders.

Mild Inactivation of RE-1 Silencing Transcription Factor (REST) Reduces Susceptibility to Kainic Acid-Induced Seizures.

RE-1 Silencing Transcription factor (REST) controls several steps in neural development by modulating the expression of a wide range of neural genes. Alterations in REST expression have been associated with the onset of epilepsy; however, whether such alterations are deleterious or represent a protective homeostatic response remains elusive. To study the impact of REST modulation on seizure propensity, we developed a tool for its negative modulation .

Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.

Optogenetics provides new ways to activate gene transcription; however, no attempts have been made as yet to modulate mammalian transcription factors. We report the light-mediated regulation of the repressor element 1 (RE1)-silencing transcription factor (REST), a master regulator of neural genes. To tune REST activity, we selected two protein domains that impair REST-DNA binding or recruitment of the cofactor mSin3a.