Deficiency of RbAp48 protein and memory loss

Memory is commonly referred to as the ability to encode, store, retain and subsequently recall information and past experiences in the human brain. This process involves many proteins, one of which is the Histone-binding protein RbAp48 (also known as RBBP4 or NURF55), encoded by the RBBP4 gene in humans.

RbAp48, also known as RBBP4 gene encodes a nuclear protein, which belongs to a highly conserved family of WD40 repeat. This gene is present in many protein complexes that are involved in Histone acetylation and deacetylation processes as well as chromatin assembly. This gene also belongs to the Mi-2/NuRD complex, also known as nucleosome remodeling deacetylase complex which plays a role in both ATP-dependent chromatin remodeling and histone deacetylase activities. This protein is also part of a co-repressor complex which is an important component of transcriptional silencing. This gene is widely available and can be found in several cellular proteins which bind directly to the retinoblastoma protein to regulate growth and cell proliferation. This protein also found in the transcriptional repression of E2F-responsive genes, which are a group of genes that encode for a family of transcription factors.

To further distinguish age-related memory loss from Alzheimer's disease (AD), a subregion of the hippocampal formation called the dentate gyrus (DG) was further studied, since it is thought to be targeted by aging. Human postmortem tissue was collected from both DG and entorhinal cortex (EC). Entorhinal cortex is a neighboring subregion unaffected by aging and known to be implicated in age-related memory loss. After normalizing the expression of EC, 17 genes were manifested due to age-related changes in the DG. Mice were used as the experimental subjects to test whether the decline of RbAp48 was also related to age-related memory loss. The results were consistent with the human studies, where the level of RbAp48 protein was much lower in adults as compared to the young. To solidify these findings, magnetic resonance imaging (MRI) was performed which revealed that occurred in the DG, corresponding to the regionally selective decreases in histone acetylation.

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