New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo.

Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were synthesized and found to up-regulate, at nanomolar concentrations, superoxide dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione peroxidase (GPX) in rat primary cortical cultures.

Neuroprotective effects of a new synthetic peptide, CMX-9236, in in vitro and in vivo models of cerebral ischemia.

NGF (nerve growth factor) and BDNF (brain-derived neurotrophic factor) are protein molecules (MW 26 and 13.6 kDa, respectively) that are neuroprotective in the middle cerebral artery occlusion (MCAO) rat stroke model. Their mechanism of action involves the activation of transcription factor AP-1 that turns on neuronal growth genes.

CMX-8933, a peptide fragment of the glycoprotein ependymin, promotes activation of AP-1 transcription factor in mouse neuroblastoma and rat cortical cell cultures.

An 8-amino acid peptide fragment (CMX-8933) of Ependymin, a glycoprotein component of the extracellular fluid and cerebrospinal fluid of goldfish brain, was synthesized and tested for its capacity to activate AP-1 transcription factor in cell cultures. Dose-response and time-course studies of AP-1's binding to DNA were carried out in neuroblastoma (NB2a/dl) and primary rat brain cortical cultures using an electrophoretic mobility shift assay (EMSA). A 13-14-fold increase in AP-1's DNA binding was obtained when NB2a cells were incubated for 4 h with 6-10 microg/ml CMX-8933.

Fatty acid derivatives of clozapine: prolonged antidopaminergic activity of docosahexaenoylclozapine in the rat.

Stable amides of clozapine derived from fatty acids prominent in cerebral tissue might enhance the central activity of clozapine and reduce its exposure to peripheral tissues. Such derivatives might enhance the safety of this unique drug, which is the only agent with securely established superior antipsychotic effectiveness, but with a risk of potentially lethal systemic toxicity. Amide derivatives of clozapine were prepared from structurally varied fatty acid chlorides and evaluated for ability to inhibit behavioral arousal in rat induced by dopamine agonist apomorphine and to induce catalepsy.