. Two key genes closely implicated with the neuropathological characteristics in Down syndrome: DYRK1A and RCAN1. BMB Rep. 2009 Jan 31;42(1):6-15. PubMed.

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  1. The overexpression DYRK1A and RCAN1, an inhibitor of calcineurin A, are thought to be involved in the neuropathology of Down syndrome. It's of interest that Liang and colleagues report that DYRK1A stabilizes the HPV16E7 oncoprotein (1). HPV16 has been associated with the development of cervical carcinoma and reduced calcineurin activity is reported in this condition (2). It's interesting that cataracts, skin wrinkling, hair loss, hyperkeratosis, and seminoma are reported in the HPV16E7 transgenics (3,4). All of these conditions are reported in Down syndrome (5). Might an HPV16 germ cell infection cause trisomy 21? Ferrer and colleagues report "Increased Dyrk1A immunoreactivity has been found in the cytoplasm and nuclei of scattered neurons of the neocortex, entorhinal cortex, and hippocampus in AD, DS, and PiD" (5). I'd like to propose that HPV16E7 may be implicated in the disease process of AD and DS.

    References:

    . DYRK1A stabilizes HPV16E7 oncoprotein through phosphorylation of the threonine 5 and threonine 7 residues. Int J Biochem Cell Biol. 2008;40(11):2431-41. PubMed.

    . Downregulation of calcineurin activity in cervical carcinoma. Cancer Cell Int. 2005 Apr 1;5(1):7. PubMed.

    . Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene. J Virol. 1996 Mar;70(3):1873-81. PubMed.

    . Very high incidence of germ cell tumorigenesis (seminomagenesis) in human papillomavirus type 16 transgenic mice. J Virol. 1991 Jun;65(6):3335-9. PubMed.

    . Testicular seminoma and Down's syndrome. Can J Urol. 2001 Feb;8(1):1203-6. PubMed.

    . Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis. 2005 Nov;20(2):392-400. PubMed.