DNA is present in the nucleus of a cell in a very highly compacted state called chromatin. Chromatin is a combination of DNA, protein and RNA. The protein component of the chromatin is composed of histones and other non-histone proteins. The basic unit of a chromatin is nucleosome and is composed of dimers of histones H2A and H2B and tetramer of H3 and H4. The histones contain a highly dynamic N-terminal tails. The N terminal tails undergo various post translational modifications such as phosphorylation, acetylation, methylation, sumoylation, ubiquitinition and so on. Acetylation occurs on the lysine residues in the N-terminal tail where the acetyl group is transferred from acetyl CoA by the enzymatic activity of histone acetyltransferases (HATs). This acetylation is a reversible reaction, where the deacetylation is performed by another group of enzymes called the histone deaectylases (HDACs). The acetylation of the histone tails induces a more relaxed chromatin conformation enhancing the accessibility of the transcription machinery and resulting in transcription activation. On the contrary, histone deacetylation compacts the chromatin and induces transcription silencing.
Balance of histone acetylation gets altered in various diseases e.g., Cancer, AIDS and neurodegenerative diseases such as Alzheimer's or Huntington's diseases. In various neurodegenerative diseases like Alzheimer, several histone acetylation marks go down in the brain. Thus, small molecule activators of histone acetyltransferases could be potential drugs for neurodegenerative diseases. However, most of these small molecule HAT activators are unable to cross the blood brain barrier, and hence, the necessity for a delivering agent/carrier for delivering the small molecule HAT activators is immense.
Recently, nanotechnology has made lots of prospects in drug delivery. However, there are no reports showcasing efficient delivery of small molecule HAT activators.
Hence, the present disclosure aims at overcoming the aforesaid drawbacks of the prior art and providing for improved and efficient HAT activator compositions.