Penningtonboyette8719

Pathologic calcium (Ca2+) signaling linked to Alzheimer's disease (AD) involves the intracellular Ca2+ release channels/ryanodine receptors (RyRs). RyRs are macromolecular complexes where the protein-protein interactions between RyRs and several regulatory proteins impact the channel function. Pharmacological and genetic approaches link the destabilization of RyRs macromolecular complexes to several human pathologies including brain disorders. In this review we discuss our recent data demonstrating that enhanced neuronal RyR2-mediated Ca2+ leak in AD is associated with post-translational modifications (hyperphosphorylation, oxidation, and nitrosylation) leading to RyR2 macromolecular complex remodeling, and dissociation of the stabilizing protein Calstabin2 from the channel. We describe RyR macromolecular complex structure and discuss the molecular mechanisms and signaling cascade underlying neuronal RyR2 remodeling in AD. We provide evidences linking RyR2 dysfunction with β-adrenergic signaling cascade that is altered in AD. RyR2 remodeling in AD leads to histopathological lesions, alteration of synaptic plasticity, learning and memory deficits. Targeting RyR macromolecular complex remodeling should be considered as a new therapeutic window to treat/or prevent AD setting and/or progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Curcumin, the complex extracted from the traditional edible herb, has a wide range of pharmacological effects. A great deal of studies has demonstrated that curcumin could protect against cerebral ischemia-reperfusion (I/R) injury. In the present study, we aimed to test the hypothesis curcumin reduces brain damage via regulating mitophagy and preserving mitochondrial function. To clarify the potential effect and mechanism of curcumin on cerebral I/R, we utilize MCAO followed by reperfusion rats and OGD/R neurons as cerebral I/R in vivo and in vitro, respectively. METHODS We determined the cellular ROS levels and mitochondrial function, including mitochondrial membrane potential (MMP), ATP levels, state 3 respiration and state 4 respiration. We also detected the levels of mitophagy by immunofluorescent staining and western blotting. RESULTS Results found curcumin decreased neurological deficit scores, infarct volume and morphological changes of neurons in rats after brain I/R injury. Curcumin also reduced the levels of ROS while increased MMP, ATP levels and state 3 respiration to prevent the impairment of mitochondrial function from cerebral I/R. Furthermore, curcumin enhanced the co-localization of LC3B and mitochondrial marker VDAC1, the ratio of LC3-II to LC3-I, improving cerebral I/R-induced mitophagy. CONCLUSION In conclusion, our results suggest that curcumin protects against cerebral I/R injury by improving mitophagy and preserving mitochondrial function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Recent studies have demonstrated that endometrial DNA methylation is essential for embryo implantation during early pregnancy. Dnmt3a is one of the key enzymes for DNA methylation and could be expressed in the endometrium regularly at this stage. OBJECTIVE AND METHODS In this study, we conditionally ablated uterine Dnmt3a using progesterone receptor-cre (Pgrcre) to define the physiological roles of Dnmt3a in female reproduction. RESULTS We found that ovarian function was not apparently altered and the number of embryo implantation sites in Dnmt3aloxP/loxP Pgrcre/+ (cKO) was not significantly varied during early pregnancy. Western blotting and immunohistochemistry results showed no difference in expression or location of the estrogen receptor (ERα) and mucin 1 (Muc1), the marker of uterine receptivity. Although the expression of decidual markers, matrix metalloproteinase-2 (Mmp2), matrix metalloproteinase-9(Mmp9), and bone morphogenetic protein-2 (Bmp2), was slightly decreased in Dnmt3a cKO females, the gross morphology of mice uteri during decidualization was not significantly influenced. In the artificial induction of the decidualization model, there was also no remarkable difference in visual observed morphology or uterine weight in Dnmt3a cKO. Lastly, a continuous breeding study showed the fertility of Dnmt3a cKO female mice was not strikingly altered. CONCLUSION Overall, these results demonstrated that although some decidual markers are expressed abnormally, conditional knockout of Dnmt3a in the uterus did not significantly affect the endometrial function during embryo implantation; the embryo could implant into the endometrium normally. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Galanin (GAL) constitutes a family of neuropeptides composed of four peptides (i) galanin (GAL), (ii) galanin-message associated peptide (GAMP), (iii) galanin-like peptide (GALP), and (iv) alarin. GAL contains 29/30 amino acids, and its biological action occurs through the interactions with its various receptors (GALR1, GALR2, and GALR3). The neuropeptide GAL regulates several physiological and pathophysiological functions in the central nervous system the peripheral nervous system, and the peripheral organs. GAL is secreted mainly by oligodendrocytes, astrocytes, and the gastrointestinal tract, and its effect depends on the interaction with its different receptors. These receptors are expressed mainly in the central, peripheral nervous systems and the intestines. OBJECTIVE The present review evaluates the role of GAL family in inflammatory diseases. find more An overview is given of the signaling and pharmacological effects due to the interaction between GAL and GALR in different cell types. The potential use of GAL as a therapeutic resource is critically discussed. CONCLUSION GAL is suggested to have an anti-inflammatory function in some situations and a pro-inflammatory function in others. The literature on GAL is controversial and currently not conclusive. This could be due to the complexity of the metabolic network signaling induced by the interactions between GAL and GALR. In the next future, GAL might be a promising therapeutic resource for several diseases, but its practical use for disease control is presently not advisable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.