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 in the aforementioned protein extracts was assayed by TRAP. As can be seen in Fig 2A (n = 5 independent experiments), telomerase activity in the FB of untreated or vehicle-treated mice was very low, while significant telomerase activity was detected 12 h post AGS-499 treatment. Quantification of telomerase activity from the TRAP assay data of five independent experiments revealed an increase of 3- (p < 0.05), 3.3- (p < 0.01) and 2.2- (p < 0.05) fold in telomerase activity in mice treated with 3, 6 and 12 mg/kg, respectively (Fig 2B). To confirm the increase in telomerase activity in the mouse FB following AGS treatment, a real time PCR-based TRAP assay was used. The results revealed that treatment of mice with AGS-499 increased telomerase activity in a dose-dependent manner. An increase of 2.4-, 3-, and 2-fold was observed when 3, 6 and 12 mg/kg of AGS 499 were injected, respectively (Fig 2C). Among the examined AGS doses, 6 mg/kg exhibited the most potent effect and therefore was used henceforth.
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.