Fig. (4).

Mutated huntingtin (mHtt) mediated Huntington pathology through making complex with HDACs. The complex formed between CREB, REST and mutant huntingtin (mHtt). Normally, Htt bonded with REST, a transcriptional repressor in the cytoplasm. Htt does not intrude with CREB phosphorylation and acetyltransferase activity of CBP which results transcriptional activation followed by neuroprotective activity. In HD, CREB phosphorylation and CBP acetyltransferase activity is inhibited by mutant huntingtin. In the nucleus, REST interacts with NRSE and BDNF transcription is repressed which results neuronal death. Whereas HDACIs are responsible for increase the CREB phosphorylation and histone acetyltransferase activity with addition of restoring BDNF expression and shows neuroprotection.