Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis.
Bottom Line: Hence, we and others hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents.The survival of telomerase-expressing cells (i.e. motor neurons), but not telomerase-deficient cells, exposed to oxidative stress was increased by AGS-499 treatment, suggesting that the AGS-499 effects are telomerase-mediated.Therefore, a controlled and transient increase in telomerase expression and activity in the brain by AGS-499 may exert neuroprotective effects.
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Show MeSH
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Mentions: Telomerase activity was determined by TRAP assay and by real time PCR TRAP using the same assay conditions as above. Telomerase activity in the FB, the BS and the SC increased with time following AGS treatment and exhibited a similar time-dependent activation to that found with TERT protein (Fig 4). As can be seen in Fig 4A–D for TRAP assay and Fig. .4E for real time PCR-based TRAP assay, telomerase activity in the cytoplasmic and nuclear extracts derived from FB and in the whole cell protein extract derived from the BS and SC exhibited a gradual increase with time, with a peak at 12 h (nucleus 2.54-fold, p <0.01; cytoplasm 2.63-fold, p <0.01), a decrease at 24 h (nucleus 2.44-fold, p <0.01; cytoplasm 1.54-fold, p <0.01) and reverting to the basal level 48 h after AGS treatment.
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.