Synaptogenix Inc (SNPX)

[runncoach]

Link to the abstract from the Aegis report today from the June 2016 Journal of Biological Chemistry. When PKCe levels are increased, synapse double, when its taken away synthesis decreases 30-44%. If you click on the link there is an interesting supplemental chart at the bottom as well.

http://www.jbc.org/content/291/32/16462

Protein Kinase C? (PKC?) Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95*
Abhik Sen1, Jarin Hongpaisan, Desheng Wang, Thomas J. Nelson and Daniel L. Alkon
+ Author Affiliations

From the Blanchette Rockefeller Neurosciences Institute, Morgantown, West Virginia 26505
?1 To whom correspondence should be addressed: Blanchette Rockefeller Neurosciences Institute, 8 Medical Center Dr., Morgantown, WV 26505. Tel.: [phone]; Fax: [phone]; E-mail address: [e-mail].
Abstract

Protein kinase C? (PKC?) promotes synaptic maturation and synaptogenesis via activation of synaptic growth factors such as BDNF, NGF, and IGF. However, many of the detailed mechanisms by which PKC? induces synaptogenesis are not fully understood. Accumulation of PSD-95 to the postsynaptic density (PSD) is known to lead to synaptic maturation and strengthening of excitatory synapses. Here we investigated the relationship between PKC? and PSD-95. We show that the PKC? activators dicyclopropanated linoleic acid methyl ester and bryostatin 1 induce phosphorylation of PSD-95 at the serine 295 residue, increase the levels of PSD-95, and enhance its membrane localization. Elimination of the serine 295 residue in PSD-95 abolished PKC?-induced membrane accumulation. Knockdown of either PKC? or JNK1 prevented PKC? activator-mediated membrane accumulation of PSD-95. PKC? directly phosphorylated PSD-95 and JNK1 in vitro. Inhibiting PKC?, JNK, or calcium/calmodulin-dependent kinase II activity prevented the effects of PKC? activators on PSD-95 phosphorylation. Increase in membrane accumulation of PKC? and phosphorylated PSD-95 (p-PSD-95S295) coincided with an increased number of synapses and increased amplitudes of excitatory post-synaptic potentials (EPSPs) in adult rat hippocampal slices. Knockdown of PKC? also reduced the synthesis of PSD-95 and the presynaptic protein synaptophysin by 30 and 44%, respectively. Prolonged activation of PKC? increased synapse number by 2-fold, increased presynaptic vesicle density, and greatly increased PSD-95 clustering. These results indicate that PKC? promotes synaptogenesis by activating PSD-95 phosphorylation directly through JNK1 and calcium/calmodulin-dependent kinase II and also by inducing expression of PSD-95 and synaptophysin.