Читать книгу Influence of FOX genes on aging and aging-associated diseases - Elena Tschumak - Страница 7

FOXP2 plays an extremely important role in neuroplasticity (Haesler et al., 2006; Ebisu et al., 2017; Konopka et al., 2009; Boeckx et al., 2014; Dodson et al., 2015; Garcia-Calero et al., 2016) and review of Wohlgemuth et al. (2014) showed that FOXP2 also provided the NMDAR-mediated neuronal plasticity affecting MAPKK and tyrosine phosphatase. The MARK is a RAS downstream effector. RAS is a a GTPase that indirectly interacts with oncological relevant ant p21 and p53 indirectly. RAS, in turn, is activated by growth factor signalling and interacts with FOXO-inhibiting PIK3. Further interaction with neuro and oncoactive Trk is also discussed. (Santos, 2011), (Mengeselt et al., 2008) It influences cell proliferation and this plays a role in the development of cancer. A direct FOXO4-p53 interaction and its importance in cell aging has been demonstrated too. (Baar et al., 2017) It would be interesting to look more closely at the role of FOXP in these processes. Possibly Fisetin, related to Qis (Zhu et al., 2017), but also FOXO4-related peptide that inhibits the PI3K/AKT/p53/p21/Serpine SCAP (Zhu et al., 2015b), recently noted to be senolytic (Baar et al., 2017) could have positive effect on cancer and aging.

Guibinga et al. showed in "Neuropathogenesis of LNS. Striatal Neurodevelopment is Dysregulated in Purine Metabolism Deficiency and Impacts DARPP-32, BDNF / TrkB Expression and Signaling: New Insights on the Molecular and Cellular Basis of Lesch-Nyhan Syndrome" (2014) that downregulating Bcl11b in HPRT-deficient cells elicited a change in DARPP-32 level in the neural stem cells. This phosphoprotein is regulated by dopamine and cAMP. Its altered level in turn led to striatal B-cell leukaemia 11b (Bcl11b). The activator of the DARPP-32 striatal BDNF / TrkB signalling pathway was highly increased in HPRT-deficient cells as well as in the striatum of the HPRT knockout mice. This protected the cells from reactive oxygen species (ROS)-mediated cell death.

There are also FOXP2 interactions with members of the histone family (H2AFX; H3f3B), two heat shock proteins (Hsp25; Hsp90a) and Calcycline-binding proteins ARHGEF9, CtBP1 and effectors Gli1, Gli2 and Gli3, EGR1, IEGs, D1R and DARPP32. In addition, FOXP2 affects NMDAR-mediated neuronal plasticity, MAPKK and tyrosine phosphatase. (Mc Auley et al., 2017)

γH2AX foci in aged HSCs is increased (Rossi et al., 2007; Beerman et al., 2014; Moehrle et al., 2015; Flach et al., 2014)