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: Motor neuron survival was assessed morphologically by Nissl staining of lumbar SC sections (L5-T10; Fig 7A) derived from SOD1 Tg mice at the age of 100 days, treated with vehicle or AGS-499 (6 mg/kg) starting at 70 days of age. Similar sections derived from untreated SOD1 Tg mouse at 70 days of age were also examined for assessing the number of motor neurons prior the beginning of the treatment. The representative micrographs in Fig 7B show that a significant loss in motor neurons in the lumbar SC is observed at the age of 100 days as compared to the pre-symptomatic stage of 70 days. At the age of 100 days, a substantial attenuation in motor neuron loss in the AGS-499-treated mice was observed as compared to the vehicle-treated mice. Counting the number of motor neurons in 10 sections from each animal revealed that the mean number of motor neurons per section in vehicle-treated animals was 26.7 ± 1.96 and 43.6 ± 4.26 in AGS-499-treated mice, an increase of 60% in motor neuron survival (Fig 7C).
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.