Fu W, Lu C, Mattson MP.
Telomerase mediates the cell survival-promoting actions of brain-derived neurotrophic factor and secreted amyloid precursor protein in developing hippocampal neurons.
J Neurosci. 2002 Dec 15;22(24):10710-9.
PubMed.
It's very interesting that Fu and colleagues report that their findings "demonstrate a requirement for telomerase in the cell survival-promoting actions of BDNF and sAPP in early postmitotic hippocampal neurons."
Kharbanda et al. (1) report that c-Abl phosphorylates human telomerase reverse transcriptase (hTERT), a telomerase component, and inhibits hTERT activity, while the Beitzinger group (2) find "expression of p73 in telomerase-positive H1299 cells results in rapid downregulation of hTERT promoter activity, hTERT mRNA expression and loss of telomerase activity."
The recent study by Alvarez et al. (3) that Aβ peptide fibrils and reactive oxygen species induce an increase of c-Abl activity in rat hippocampal neurons as well as an increase in nuclear p73 protein levels, and that the neuronal cell death induced by Aβ was prevented by Gleevec, would seem to add further to the puzzle.
The Wilson group report that in AD hippocampus, increased levels of p73 are located in the nucleus of pyramidal neurons and p73 is located in dystrophic neurites and cytoskeletal pathology.
Is Aβ a down-regulator of telomerase activity?
Bakalova et al. have reported that inhibition of c-Abl results in increased telomerase. Gleevec, a c-Abl inhibitor (and an inhibitor of amyloid-β production; see Netzer et al., 2003) would then be expected to increase telomere length. Of further interest is the finding by Epel and colleagues that life stress is associated with telomere shortening. They suggest that the stress hormone response may cause oxidative stress. Might we then expect increased expression of c-Abl in this group?
Comments
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It's very interesting that Fu and colleagues report that their findings "demonstrate a requirement for telomerase in the cell survival-promoting actions of BDNF and sAPP in early postmitotic hippocampal neurons."
Kharbanda et al. (1) report that c-Abl phosphorylates human telomerase reverse transcriptase (hTERT), a telomerase component, and inhibits hTERT activity, while the Beitzinger group (2) find "expression of p73 in telomerase-positive H1299 cells results in rapid downregulation of hTERT promoter activity, hTERT mRNA expression and loss of telomerase activity."
The recent study by Alvarez et al. (3) that Aβ peptide fibrils and reactive oxygen species induce an increase of c-Abl activity in rat hippocampal neurons as well as an increase in nuclear p73 protein levels, and that the neuronal cell death induced by Aβ was prevented by Gleevec, would seem to add further to the puzzle.
The Wilson group report that in AD hippocampus, increased levels of p73 are located in the nucleus of pyramidal neurons and p73 is located in dystrophic neurites and cytoskeletal pathology.
Is Aβ a down-regulator of telomerase activity?
Bakalova et al. have reported that inhibition of c-Abl results in increased telomerase. Gleevec, a c-Abl inhibitor (and an inhibitor of amyloid-β production; see Netzer et al., 2003) would then be expected to increase telomere length. Of further interest is the finding by Epel and colleagues that life stress is associated with telomere shortening. They suggest that the stress hormone response may cause oxidative stress. Might we then expect increased expression of c-Abl in this group?
See also:
Michaela Beitzinger
References:
Kharbanda S, Kumar V, Dhar S, Pandey P, Chen C, Majumder P, Yuan ZM, Whang Y, Strauss W, Pandita TK, Weaver D, Kufe D. Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase. Curr Biol. 2000 May 18;10(10):568-75. PubMed.
Alvarez AR, Sandoval PC, Leal NR, Castro PU, Kosik KS. Activation of the neuronal c-Abl tyrosine kinase by amyloid-beta-peptide and reactive oxygen species. Neurobiol Dis. 2004 Nov;17(2):326-36. PubMed.
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