Alzheimer's disease and HIV associated dementia related genes: I. location and function

Abstract

Alzheimer's disease (AD), the most common cause of dementia, has few clinical similarities to HIV-1-associated dementia (HAD). However, genes were identified related among these dementias. Discovering correlations between gene function, expression, and structure in the human genome continues to aid in understanding the similarities between pathogenesis of these two dementing disorders. The current work attempts to identify relationships between these dementias in spite of their clinical differences, based on genomic structure, function, and expression. In this comparative study, the NCBI Entrez Genome Database is used to detect these relationships. This approach serves as a model for future diagnosis and treatment in the clinical arena as well as suggesting parallel pathways of disease mechanisms. Identifying a correlation among expression, structure, and function of genes involved in pathogenesis of these dementing disorders, may assist to understand better their interaction with each other and the human genome.

Common Transcriptional Signatures in Brain Tissue from Patients with HIV-Associated Neurocognitive Disorders, Alzheimer’s Disease, and Multiple Sclerosis

“…This notion is supported by recent proteomic analysis of postmortem frontal cortex tissues from HIV positive patients with or without HAD, which revealed aberrant expression of proteins involved in glycolysis and oxidative phosphorylation specifically in HAD tissues and noted similar pathway changes in other dementia conditions including Alzheimer’s and Parkinson’s diseases (Zhou et al 2010). Broader patterns of similarity between HAND and diseases such as AD and MS were suggested based on review of macrophage/microglia and astrocyte functions in neuropathogenesis (Minagar et al 2002), review of dysregulation of specific genes in these pathologies (Minagar et al 2004), and bioinformatics-aided analysis of potential parallels in chromosomal localization, expression and function of dementia-associated genes between HAND and AD (Shapshak et al 2008). Indeed, a recent review by Noorbakhsh et al presented a convincing case for the power of integrative analysis of data-rich studies involving functional genomics, proteomics, and other systems biology approaches in discerning convergent pathways of human neuropathogenesis (Noorbakhsh et al 2009).…”

Molecular Epigenetics, Chromatin, and NeuroAIDS/HIV: Translational Implications

“…Several hypotheses resulted from this work including that the expression of the genes identified was perturbed by the abused drug, cocaine, and HIV-1 proteins, Tat and Env; that these genes were influenced in transcriptionally isolated groups; and that transcription overload (coerced expression due to cocaine and HIV-1 proteins) may result in damage to the chromosome's organization and control of the chromatin transcription machinery (chromatin remodeling). It should be noted that an association of HIV and host-related genes was found in additional studies [34,35]. …”

Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia

“…In addition, an unannotated Affymetrix chip probe coded 15588882_at was expressed highly at the first sampling occasion, which was annotated more recently to the gene HTATSF1P2 . Little is known about this gene, except that it has been reported to show sequence homologies to another gene of which there is also only very scant information available, termed HIV TAT specific factor 1, claimed to be a co‐factor required for Tat activation of HIV‐1 transcription (gene ID: 401233) We therefore wanted to verify by an independent method that this putative gene is actually transcribed in our patient, and secondly, to determine whether this gene transcript is a constituent of other cell types than blood leucocytes. Figure shows the TaqMan qPCR analysis of mRNA expression of the HTATSF1P2 gene in the patient relative to that of a normal child, verifying that it was up‐regulated at all three sampling occasions, as was implicated by the array analyses.…”