👤 Patrik Simko

P2X receptors, a family of ATP-gated ion channels, are increasingly recognized as key contributors to the pathophysiology of major depressive disorder. Among them, P2X7 plays a central role in stress-induced neuroinflammation by driving microglial activation, inflammasome signaling, and downstream reductions in BDNF and neuroplasticity. Additional P2X subtypes, including P2X4, further modulate neuronal and glial communication relevant to mood regulation. Evidence from animal models, human genetic studies, and early therapeutic trials supports the involvement of P2X signaling in depressive phenotypes and highlights P2X7 antagonists as promising candidates for novel antidepressant strategies. Overall, targeting P2X receptors offers a mechanistically distinct approach to understanding and treating depression. Show less

Despite an enormous success in reducing morbidity and mortality in cardiovascular disease (CVD), statins and modern antihypertensive medications are not universally effective. Research has focused on potential molecular targets in dyslipidemia. Decades-long, expensive trial with CETP (cholesterylester transfer protein) inhibitor evacetrapib, came in April 2016 to crash landing. Despite dramatic improvement in "good" HDL-cholesterol and decline in "bad" LDL-C, the effect of evacetrapib in CVD patients was comparable to placebo. Notwithstanding failure in this molecular target field, results with another agent the PCSK9 inhibitor, may identify the molecular site that would normalize dyslipidemia, without harming physiologically essential lipids (Fig. 2, Ref. 19). Show less