Accelerated aging and aging process in the brain.

One of the approaches to the research of the problem of aging is the study of genetic pathologies leading to accelerated aging, such as the Hutchinson-Gilford progeria syndrome, Werner syndrome, and Down syndrome. Probably, this approach can be used in an attempt to understand the neuronal mechanisms underlying normal and pathological brain aging. The analysis of the current state of scientific knowledge about these pathologies shows that in the Hutchinson-Gilford progeria and Werner syndrome, the rate of brain aging is significantly lower than the rate of whole body aging, whereas in Down syndrome, the brain ages faster than other organs due to amyloid-beta accumulation and chronic oxidative stress in the brain tissue. The main point of a previously proposed hypothesis is that the aging of higher animals and humans is associated with an increased level of reactive oxygen species in mitochondria with age, which activates apoptosis, thus reducing the number of functioning cells.

Structural organization of the human complexin 2 gene (CPLX2) and aspects of its functional activity.

We report here on the in vitro and in silico characterization of the organization of the human complexin 2 (CPLX2) gene. This encodes for a protein of 134 amino acid residues, contains five exons, is localized on human chromosome 5q35.3, and spans more than 87 kb. We performed in silico analysis of the CPLX2 5' untranslated region (UTR) and propose an alternative variant of the gene transcript. Compared to the mRNA reported earlier [McMahon, H.T., Missler, M., Li, C., Sudhof, T.C., 1995. Complexins: cytosolic proteins that regulate SNAP receptor function. Cell 83, 111-119.], this transcript bears a partly altered 5'-UTR associated with the same open reading frame. Both CPLX2 transcripts share exons III-V; the alternative transcript is devoid of exons I and II, and includes exon A instead. Exon A is localized within CPLX2 intron 2 about 7 kb upstream to exon III. Using reverse transcription polymerase chain reaction (RT-PCR) we detected both types of transcripts in human brain mRNA. In silico data suggest that two putative alternative TATA-less promoter regions separated by 74 kb govern the expression of two CPLX2 transcripts. Several potential transcription start sites were detected by primer extension for each of two alternative CPLX2 transcripts. The relative abundance of the alternative transcripts was investigated in human and rat forebrain, cerebellum, and hippocampus. Whereas both transcripts were detected in human and rat brain, their expression levels were found to vary significantly among the regions investigated. The organization of CPLX2 transcripts is conserved in humans and rodents.