Development of a Highly Selective Ferroptosis Inducer Targeting GPX4 with 2-Ethynylthiazole-4-carboxamide as Electrophilic Warhead.

A highly selective ferroptosis inducer with drug-like properties can significantly advance the research on inducing ferroptosis for anticancer treatment. We previously reported a highly active GPX4 inhibitor , but its activity and stability need further improvement. In this work, a novel GPX4 inhibitor with more potent cytotoxicity (IC = 0.

Activation of phospholipase-Cγ and protein kinase C signal pathways helps the survival of spinal motoneurons injured by root avulsion.

The signaling transduction processes involved in avulsion-induced motoneuron (MN) death have not been elucidated. Using the brachial plexus root avulsion rat model, we showed that avulsion-activated phosphorylation of phospholipase-Cγ (PLCγ) and protein kinase C (PKC) occurred in injured spinal MNs within 72 h of injury. Moreover, some MNs positive for PLCγ and PKC are also positive for avulsion-induced neuronal nitric oxide synthase (nNOS).

The diversity of nNOS gene expression in avulsion-injured spinal motoneurons among laboratory rodents.

Rats, mice, and hamsters are commonly used laboratory rodents in the experimental modeling strategies of avulsion-induced motoneuron degenerations. It is necessary to study the species-specific gene expression in spinal cord in response to avulsion. We carried out the brachial roots avulsion in all animals and compared the survival and nNOS gene expression in injured motoneurons and spinal segments among the three species.