Leveraging PARP-1/2 to Target Distant Metastasis.

Poly (ADP-Ribose) Polymerase (PARP) inhibitors have changed the outcomes and therapeutic strategy for several cancer types. As a targeted therapeutic mainly for patients with mutations, PARP inhibitors have commonly been exploited for their capacity to prevent DNA repair. In this review, we discuss the multifaceted roles of PARP-1 and PARP-2 beyond DNA repair, including the impact of PARP-1 on chemokine signalling, immune modulation, and transcriptional regulation of gene expression, particularly in the contexts of angiogenesis and epithelial-to-mesenchymal transition (EMT).

Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina.

Cell replacement therapies may be key in achieving functional recovery in neurodegenerative optic neuropathies diseases such as glaucoma. One strategy that holds promise in this regard is the use of human embryonic stem cell and induced pluripotent stem-derived retinal ganglion cells (hRGCs). Previous hRGC transplantation studies have shown modest success.

Lessons learned from the evinacumab trials in the treatment of homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a life-threatening disease characterized by extremely elevated LDL cholesterol (LDL-C) levels which result in premature atherosclerotic cardiovascular disease. As conventional lipid-lowering therapies, which mainly depend on LDL receptors for LDL particle clearance, remain insufficient for reaching the recommended LDL-C levels in HoFH, agents acting independently of LDL receptors, such as ANGPTL3 inhibitors, constitute a promising target. Evinacumab, a monoclonal antibody directed against ANGPTL3, was approved in the USA in 2021 for treating patients with HoFH.

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice.

The nitric oxide-guanylyl cyclase-1-cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase () develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration.

Endothelial deletion of PKCδ prevents VEGF inhibition and restores blood flow reperfusion in diabetic ischemic limb.

Aims: Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling.