| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2201142 | Neurochemistry International | 2011 | 9 Pages |
Histone deacetylases (HDACs) play a pivotal role in epigenetic regulation of transcription and homeostasis of protein acetylation in histones and other proteins involved in chromatin remodeling. Histone hypoacetylation and transcriptional dysfunction have been shown to be associated with a variety of neurodegenerative diseases. More recently, neuron specific overexpression of HDAC2 has been shown to modulate synaptic plasticity and learning behavior in mice. However, the role of HDAC2 in development of HIV-associated neurocognitive disorders (HAND) is not reported. Herein we report that HIV-1 Tat protein upregulate HDAC2 expression in neuronal cells leading to transcriptional repression of genes involved in synaptic plasticity and neuronal function thereby contributing to the progression of HAND. Our results indicate upregulation of HDAC2 by Tat treatment in dose and time dependant manner by human neuroblastoma SK-N-MC cells and primary human neurons. Further, HDAC2 overexpression was associated with concomitant downregulation in CREB and CaMKIIa genes that are known to regulate neuronal activity. These observed effects were completely blocked by HDAC2 inhibition. These results for the first time suggest the possible role of HDAC2 in development of HAND. Therefore, use of HDAC2 specific inhibitor in combination with HAART may be of therapeutic value in treatment of neurocognitive disorders observed in HIV-1 infected individuals.
Research highlights► HIV-1 Tat protein upregulates HDAC2 expression in neurons. ► HDAC2 upregulation leads to downregulation of CREB and CaMKIIa. ► CREB and CaMKIIa play an important role in regulating neuronal function. ► Knockdown of HDAC2 inhibits the effect of Tat protein on CREB and CaMKIIa. ► Possible role of HDAC2 in development of HIV-associated neurocognitive disorder.
