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Hayashi Y, Yoshida M, Yamato M, Ide T, Wu Z, Ochi-Shindou M, Kanki T, Kang D, Sunagawa K, Tsutsui H, Nakanishi H. Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice. J Neurosci. 2008 Aug 20;28(34):8624-34. PubMed.
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Comments
It's interesting that TFAM can prevent age-dependent memory impairment and loss of neuronal function when overexpressed in transgenic mice. Telmisartan increases expression of TFAM and MTOC1 and has been found to prevent cognitive decline following intracerebroventricular injection of Aβ1-40 (1,2).
Perhaps further reason to suspect benefit with Telmisartan therapy in AD and ALS is provided by Baden and colleagues who report that Telmisartan inhibits methylglyoxal induced caspase-3 activation. Methylglyoxal has been implicated in the formation of amyloid plaques and neurofibrillary tangles in AD. Rohn suggests that caspase-cleaved TDP-43 is a major pathological finding in AD (3,4,5).
References:
Sugimoto K, Qi NR, Kazdová L, Pravenec M, Ogihara T, Kurtz TW. Telmisartan but not valsartan increases caloric expenditure and protects against weight gain and hepatic steatosis. Hypertension. 2006 May;47(5):1003-9. PubMed.
Mogi M, Li JM, Tsukuda K, Iwanami J, Min LJ, Sakata A, Fujita T, Iwai M, Horiuchi M. Telmisartan prevented cognitive decline partly due to PPAR-gamma activation. Biochem Biophys Res Commun. 2008 Oct 24;375(3):446-9. PubMed.
Baden T, Yamawaki H, Saito K, Mukohda M, Okada M, Hara Y. Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium. Biochem Biophys Res Commun. 2008 Aug 22;373(2):253-7. PubMed.
Kuhla B, Lüth HJ, Haferburg D, Boeck K, Arendt T, Münch G. Methylglyoxal, glyoxal, and their detoxification in Alzheimer's disease. Ann N Y Acad Sci. 2005 Jun;1043:211-6. PubMed.
Rohn TT. Caspase-cleaved TAR DNA-binding protein-43 is a major pathological finding in Alzheimer's disease. Brain Res. 2008 Sep 4;1228:189-98. PubMed.
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