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: Previous studies demonstrated telomerase activity and expression in various adult (8–10 weeks) mouse central nervous system (CNS) regions (Caporaso et al, 2003; Flanary and Streit, 2003; Fu et al, 2000; Lee et al, 2009). We have synthesized novel triaryl compounds that increased telomerase expression in various human cell lines and in vivo in animal models (patents WO 2008/149353, WO 2008/149345, Priel et al) One of these compounds, designated AGS-499 (chemical formula in Fig 1A), was examined for its ability to increase telomerase expression in the mouse brain.
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.