• With rare exceptions the biological role of

  2022-01-03

  

  With rare exceptions, the biological role of γ-secretase cleavage of substrates other than Notch 1 has been ignored during proof of concept preclinical repurposing studies. For example, in the GSI AD trial, many individuals noted changes in hair color, apparently due to inhibition of tyrosinase, ano

• Canonical and non canonical Wnt signaling pathways play esse

  2022-01-03

  

  Canonical and non-canonical Wnt signaling pathways play essential roles in various cellular activities, including cell fate determination, proliferation, migration and gene expression [57]. The canonical Wnt pathway (β-catenin dependent pathway), is activated by the binding of Wnt ligands, leading t

• A common feature of ferroptosis is the iron dependent

  2022-01-03

  

  A common feature of ferroptosis is the iron-dependent accumulation of lipid-ROS and the subsequent depletion of polyunsaturated fatty ion channel phospholipids (PUFA-PLs) [118]. The PUFA chains of membrane lipids are more susceptible to both enzymatic and non-enzymatic oxidation, which results in P

• The NGS of six Southern Brazil patients revealed

  2022-01-03

  

  The NGS of six Southern Brazil patients revealed three different variants: c.472C > T (p.Arg158Trp); c.958G>A (p.Gly320Arg) and c.986T>C (p.Leu329Pro) (Table 2). The amino acids involved in these substitutions were evolutionarily conserved in different species (Fig. 1B). The amino inositol phosphata

• Recently the classical view of the compartmentalization of t

  2022-01-03

  

  Recently, the classical view of the compartmentalization of the plant isoprenoid metabolism has been re-evaluated, following the demonstration of the partial peroxisomal localization of the mevalonic gsk-3 (MVA) pathway, generally regarded as cytosolic. Using GFP-tagging approaches, the last two en

• In cancer cells HIF upregulates HK II expression by binding

  2022-01-03

  

  In cancer cells, HIF-1α upregulates HK-II expression by binding to the hypoxia-responsive element in the HK-II promoter region to adapt to hypoxic conditions [20]. In the present study, we observed that mangiferin transiently increased HIF-1α expression in endothelial cells, suggesting another possi

• Acknowledgement This work was supported by grants from

  2022-01-03

  

  Acknowledgement This work was supported by grants from the National Natural Science Foundation of China (No.81802749), Shenzhen Healthcare Research Project (No.SZBC2017029), the Science and Technology Foundation of Shenzhen (JCYJ20170412155231633, JSGG20170414104216477), National Key Research and D

• In diseased blood vessels increased production of

  2021-12-31

  

  In diseased blood vessels, increased production of reactive oxygen species (ROS), such as peroxynitrite, superoxide, and hydrogen peroxide, have been found [[53], [54], [55]]. Peroxynitrite was suggested to alter the redox state of sGC [53] while hydrogen peroxide interfered with the action of NO bu

• Previous studies have shown that Cu I

  2021-12-31

  

  Previous studies have shown that Cu(I) neurotoxicity includes induction of ROS with involvement of the NF-kB pathway and apoptosis (Butterworth, 2010) and that, in its Cu(I) state, Cu(I) alters microglia phenotype and inhibits nitric oxide release (Rossi-George et al., 2012). Cu(I) has a great affin

• In the present study we characterized the expression of

  2021-12-31

  

  In the present study, we characterized the expression of glucose transporters in the developing and adult mouse lens and showed that GLUT1 is the primary transporter expressed in the lens epithelium. We found that mice with a homozygous deletion of Slc2a1 from the lens epithelium developed cataracts

• Importance of glucokinase in glucose homeostasis and a

  2021-12-31

  

  Importance of glucokinase in glucose homeostasis and a possibility to change its activity using the activators define the scientific interest in the development of new allosteric activators of GK (Liu et al., 2012, Pfefferkorn et al., 2011, Waring et al., 2013, Behera et al., 2015). Activation of gl

• Our results revealed that when subjected

  2021-12-31

  

  Our results revealed that when subjected to intravenous glucose tolerance tests, the RIP-Gcgr mice showed enhanced glucose tolerance and increased beta cell function, which is in agreement with the findings of Gelling et al. [6]. However, we also show that there is a reduced responsiveness of the be

• Gap junction intercellular communication GJIC facilitates th

  2021-12-30

  

  Gap junction intercellular communication (GJIC) facilitates the exchange of ions, metabolites, Ca2+, inositol phosphates, and/or cyclic nucleotides of up to 1.8 kD in size between GDC-0032 receptor through contact-dependent mechanisms [3,4]. Oocyte growth and development (as depicted in Fig. 1) dep

• In general substrates that undergo regulated intramembrane

  2021-12-30

  

  In general substrates that undergo regulated intramembrane proteolysis are initially cleaved in the extracellular domain by sheddases such as TACE (TNFα converting enzyme) or ADAM (a disintegrin and metalloproteinase domain)/α-secretase, or by aspartyl proteases, such as BACE/β-secretase, before cle

• br Secretase modulators a loss

  2021-12-30

  

  γ-Secretase modulators: a loss of pharmacology? A lack of translation from in vitro to in vivo pharmacology is an unresolved issue among most GSMs. R-flurbiprofen was tested in clinical trials, however, it did not achieve statistical significance on either of its primary endpoints – cognition or

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