Neurodegenerative Diseases.
Activated protein C and 3K3A-Activated Protein C have been shown in animal studies to be effective in Amyotrophic Lateral Sclerosis, Parkinson's Disease and Multiple Sclerosis.
The NVP-400 modified series of the NVP-202 native peptide is being developed as a weekly SubQ injection for the treatment of ALS and Parkinson's Disease.
APC binds to the EPCR located in caveolae. Caveolae translocate the endothelium and allow deposition of APC across the BBB, consistent with the results reported in this issue by Zhong et al. Once across the BBB, APC can dissociate from EPCR and signal neuronal cells through activation of PAR1 in a process dependent on PAR3, and this in turn increases the phosphorylation of the nuclear transcription factor Sp1, thereby downregulating the production of mutant SOD1 (mSOD1), a mediator of neuronal damage in this animal model of familial ALS. As described by Zhong et al., APC can also provide neuroprotective effects by reducing leakage through the BBB, inhibiting release of inflammatory cytokines from microglia as well as lessening the oxidative damage to neurons by Hb products entering the extravascular space through the endothelium.
Esmon et al. JCI, 2015.