Synthesis and biological evaluation of strained unusual amino acid containing tetrapeptides as potential antidepressant agents.

Strained unusual amino acid derived tetrapeptides were synthesized as mimics of GLYX-13, a clinical candidate for neuroprotective and anti-depressant properties, were studied. The synthesized compounds were screened for neurite growth and anti-depressant properties in vitro and in vivo respectively comparing with the parent GLYX-13 compound. Neurite growth property was assessed by neurite length and anti-depressant property by percentage of immobility in forced swim test, a behavioural assay. Mechanistic insights about protein-ligand interactions were obtained using molecular docking study. Based on the in vitro and in vivo screening data and molecular docking study, a new analogue of GLYX-13, Compound 11a has been found to be as good as the parent compound in all respects.

Epigenetic regulatory mechanisms in stress-induced behavior.

Stress response is considered to have adaptive value for organisms faced with stressful condition. Chronic stress however adversely affects the physiology and may lead to neuropsychiatric disorders. Repeated stressful events in animal models have been shown to cause long-lasting changes in neural circuitries at molecular, cellular, and physiological level, leading to disorders of mood as well as cognition. Molecular studies in recent years have implicated diverse epigenetic mechanisms, including histone modifications, DNA methylation, and noncoding RNAs, that underlie dysregulation of genes in the affected neural circuitries in chronic stress-induced pathophysiology. A review of the myriad epigenetic regulatory mechanisms associated with neural and behavioral responses in animal models of stress-induced neuropsychiatric disorders is presented here. The review also deals with clinical evidence of the epigenetic dysregulation of genes in psychiatric disorders where chronic stress appears to underlie the etiopathology.