Cell Signaling

Traumatic brain injury (TBI) poses a significant global health challenge, where secondary injury processes driven by oxidative stress and metabolic crisis are key determinants of poor neurological outcomes, yet lack effective treatments. This review synthesizes emerging evidence on a novel neuroprotective pathway—the thioredoxin-1 (Trx1)–ataxia-telangiectasia mutated (ATM)–pentose phosphate pathway (PPP) axis. 

Cell signaling represents a highly coordinated molecular dialogue that governs cellular behavior and tissue homeostasis. Among its many facets, redox signaling has emerged as a pivotal mechanism, transforming our understanding of reactive oxygen species (ROS) from mere metabolic byproducts to essential messengers [1]. Historically associated with oxidative stress and cellular damage, ROS are now recognized as regulators of physiological processes through reversible oxidation of cysteine residues in proteins.

The evolutionary origin of mitochondria remains a challenging problem, closely linked to the emergence of eukaryotic cells, a process known as eukaryogenesis. Regardless of how primordial mitochondria truly evolved, mitochondria have traditionally been viewed as bioenergetic organelles with primary functions of ATP production and metabolic support. They are classically known as the ‘powerhouse’ of the cells. In aging biology, this view has often been paired with an emphasis on mitochondrial dysfunction and oxidative imbalance and stress. 

Selective generation of hydrogen peroxide (H₂O₂) in malignant cells is a mechanistically well-supported but clinically unproven strategy in oncology. We argue that further progress in this field depends less on the identification of additional, nonspecific H₂O₂-generating compounds than on five interlocking requirements