Protein Kinase C: Targets to Regenerate Brain Injuries?

Acute or chronic injury to the central nervous system (CNS), causes neuronal death and irreversible cognitive deficits or sensory-motor alteration. Despite the capacity of the adult CNS to generate new neurons from neural stem cells (NSC), neuronal replacement following an injury is a restricted process, which does not naturally result in functional regeneration. Therefore, potentiating endogenous neurogenesis is one of the strategies that are currently being under study to regenerate damaged brain tissue. The insignificant neurogenesis that occurs in CNS injuries is a consequence of the gliogenic/non-neurogenic environment that inflammatory signaling molecules create within the injured area. The modification of the extracellular signals to generate a neurogenic environment would facilitate neuronal replacement. However, in order to generate this environment, it is necessary to unearth which molecules promote or impair neurogenesis to introduce the first and/or eliminate the latter. Specific isozymes of the protein kinase C (PKC) family differentially contribute to generate a gliogenic or neurogenic environment in injuries by regulating the ADAM17 mediated release of growth factor receptor ligands. Recent reports describe several non-tumorigenic diterpenes isolated from plants of the Euphorbia genus, which specifically modulate the activity of PKC isozymes promoting neurogenesis. Diterpenes with 12-deoxyphorbol or lathyrane skeleton, increase NPC proliferation in neurogenic niches in the adult mouse brain in a PKCb dependent manner exerting their effects on transit amplifying cells, whereas PKC inhibition in injuries promotes neurogenesis. Thus, compounds that balance PKC activity in injuries might be of use in the development of new drugs and therapeutic strategies to regenerate brain injuries

Modelling suggests ABO histo-incompatibility may substantially reduce SARS-CoV-2 transmission

Several independent datasets suggest blood type A is over-represented and type O under-represented among COVID-19 patients. However, blood group antigens appear not to be conventional susceptibility factors in that they do not affect disease severity, and the relative risk to non-O individuals is attenuated when population prevalence is high. Here, I model a scenario in which ABO transfusion incompatibility reduces the chance of a patient transmitting the virus to an incompatible recipient – thus in Western populations type A and AB individuals are “super-recipients” while type O individuals are “super-spreaders”. This results in an offset in the timing of the epidemic among individuals of different blood types, and an increased relative risk to type A/AB patients that is most pronounced during early stages of the epidemic. However, once the majority of any given population is infected, the relative risk to each blood type approaches unity. Published data on COVID-19 prevalence from regions in the early stages of the SARS-CoV-2 epidemic suggests that if this model holds true, ABO incompatibility reduces virus transmissibility by at least 60 %. Exploring the implications of this model for vaccination strategies shows that paradoxically, targeted vaccination of either high-susceptibility type A/AB or “super-spreader” type O individuals is less effective than random vaccination at blocking community spread of the virus. Instead, the key is to maintain blood type diversity among the remaining susceptible individuals. Given the good agreement between this model and observational data on disease prevalence, the underlying biochemistry urgently requires experimental investigation

Propriétés interfaciales d'une protéine membranaire: la(Na+ + K+) adénosine triphosphatase

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Cationic atmosphere and cation competition binding at negatively charged membranes: pathological implications of aluminum.

Binding of cations to membranes may be the basis for explaining some of the effects of several neurotoxic cations. The binding of Al3+ and the displacement of Ca2+ by Al3+ is studied with the aid of a simple mathematical approach described here and giving the same results when compared to the mathematical formalism described by Nir and Bentz. The method allows the simulation of membranes with low surface charge densities that are relevant for biochemical and pathological implications. Fluorescence quenching of the phospholipid analogue 1-palmitoyl-2-nitrobenzoxadiazol amino caproyl- phosphatidyl choline (C6-NBD-Ptd Cho) embedded in phosphatidyl serine membranes is used to determine the competition between calcium and aluminum for binding. The effect of aluminum in the presence of chelating agents is also studied by quenching experiments. Finally, inhibition of 45Ca2+ binding to phosphatidyl serine has also been investigated in a two-phase system.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe