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Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis.

Eitan E, Tichon A, Gazit A, Gitler D, Slavin S, Priel E - EMBO Mol Med (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

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Expression of TERT protein in the FB and BS of SOD1 Tg mice before and after disease onset and the effect of AGS-499 treatment on its expressionNuclear and cytoplasmic proteins extracts were prepared from the FB and BS regions (A,B,D) and total RNA was extracted from the BS regions (C).A-B. Extracts derived from SOD1 Tg mice at the pre-symptomatic stage (40–70 days), after disease onset (100 days), before death (neurological score 5) were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.C. TERT RNA transcripts were detected by Real time PCR, normalized to β-actin and the quantification of TERT expression was calculated relatively to the value obtained for mouse embryonic brain (E17). The results are mean ± s.e.m., n = 3–9 per group, Student's t-test *1p = 0.063, *2p = 0.006.D. Extracts derived from AGS-499 treated or vehicle treated SOD1 mice at the age of 100 days were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.
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fig08: Expression of TERT protein in the FB and BS of SOD1 Tg mice before and after disease onset and the effect of AGS-499 treatment on its expressionNuclear and cytoplasmic proteins extracts were prepared from the FB and BS regions (A,B,D) and total RNA was extracted from the BS regions (C).A-B. Extracts derived from SOD1 Tg mice at the pre-symptomatic stage (40–70 days), after disease onset (100 days), before death (neurological score 5) were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.C. TERT RNA transcripts were detected by Real time PCR, normalized to β-actin and the quantification of TERT expression was calculated relatively to the value obtained for mouse embryonic brain (E17). The results are mean ± s.e.m., n = 3–9 per group, Student's t-test *1p = 0.063, *2p = 0.006.D. Extracts derived from AGS-499 treated or vehicle treated SOD1 mice at the age of 100 days were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.

Mentions: Examination of the expression of mTERT transcripts in the BS region and of mTERT protein in the FB and the BS regions of SOD1 Tg mice was performed at the following disease stages: pre-symptomatic (40–70 days), after the onset of disease (100 days), and at the terminal stage (neurological score 5). Untreated SOD1 Tg mice exhibited a significant decrease in mTERT protein (Fig 8A and B) and a three- to fourfold decrease in the expression of mTERT RNA transcripts (Fig 8C) during the progression of the disease. In contrast, AGS-treated SOD1 mice preserved the expression of mTERT protein in the FB and BS regions at the age of 100 days, after the onset of disease (Fig 8D).


Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis.

Eitan E, Tichon A, Gazit A, Gitler D, Slavin S, Priel E - EMBO Mol Med (2012)

Expression of TERT protein in the FB and BS of SOD1 Tg mice before and after disease onset and the effect of AGS-499 treatment on its expressionNuclear and cytoplasmic proteins extracts were prepared from the FB and BS regions (A,B,D) and total RNA was extracted from the BS regions (C).A-B. Extracts derived from SOD1 Tg mice at the pre-symptomatic stage (40–70 days), after disease onset (100 days), before death (neurological score 5) were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.C. TERT RNA transcripts were detected by Real time PCR, normalized to β-actin and the quantification of TERT expression was calculated relatively to the value obtained for mouse embryonic brain (E17). The results are mean ± s.e.m., n = 3–9 per group, Student's t-test *1p = 0.063, *2p = 0.006.D. Extracts derived from AGS-499 treated or vehicle treated SOD1 mice at the age of 100 days were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.
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Related In: Results  -  Collection

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fig08: Expression of TERT protein in the FB and BS of SOD1 Tg mice before and after disease onset and the effect of AGS-499 treatment on its expressionNuclear and cytoplasmic proteins extracts were prepared from the FB and BS regions (A,B,D) and total RNA was extracted from the BS regions (C).A-B. Extracts derived from SOD1 Tg mice at the pre-symptomatic stage (40–70 days), after disease onset (100 days), before death (neurological score 5) were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.C. TERT RNA transcripts were detected by Real time PCR, normalized to β-actin and the quantification of TERT expression was calculated relatively to the value obtained for mouse embryonic brain (E17). The results are mean ± s.e.m., n = 3–9 per group, Student's t-test *1p = 0.063, *2p = 0.006.D. Extracts derived from AGS-499 treated or vehicle treated SOD1 mice at the age of 100 days were analysed (25 µg) by Western blotting using anti TERT or anti-β actin antibodies.
Mentions: Examination of the expression of mTERT transcripts in the BS region and of mTERT protein in the FB and the BS regions of SOD1 Tg mice was performed at the following disease stages: pre-symptomatic (40–70 days), after the onset of disease (100 days), and at the terminal stage (neurological score 5). Untreated SOD1 Tg mice exhibited a significant decrease in mTERT protein (Fig 8A and B) and a three- to fourfold decrease in the expression of mTERT RNA transcripts (Fig 8C) during the progression of the disease. In contrast, AGS-treated SOD1 mice preserved the expression of mTERT protein in the FB and BS regions at the age of 100 days, after the onset of disease (Fig 8D).

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.

View Article: PubMed Central - PubMed

Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Show MeSH
Related in: MedlinePlus