Globin Proteins in Neurophysiological Contexts

Globin proteins, long recognised for their roles in oxygen transport and storage, have emerged as versatile players in the nervous system. Neuroglobin, predominantly expressed in neurons, exhibits a high affinity for oxygen and displays redox‐sensitive ligand binding that may protect against hypoxic or oxidative stress. Cytoglobin, found in glial and vascular cells, couples oxygen binding with nitric oxide metabolism and redox signalling, thereby influencing vascular tone, neurovascular coupling and organ development. More recently identified members of the superfamily, such as androglobin, combine globin domains with additional modules, suggesting specialised roles in nitric oxide homeostasis and cellular signalling. Collectively, these proteins intersect with diverse neurophysiological processes: they modulate oxygen and nitric oxide availability, safeguard against reactive oxygen and nitrogen species, support mitochondrial function and participate in cell‐to‐cell communication. Dysfunction or dysregulation of globin expression and activity is increasingly linked to developmental anomalies, cerebrovascular disorders, neurodegeneration and cancer, emphasising their global significance and therapeutic potential.

Research from Nature Portfolio

Recent studies have revealed that cytoglobin acts as a critical regulator of a nitric oxide synthase–soluble guanylate cyclase–cGMP signalling axis during vertebrate development. In zebrafish, loss of cytoglobin disrupts ciliary structure and motility within the Kupffer’s vesicle, leading to aberrant left–right patterning that is rescued by exogenous nitric oxide donors or guanylate cyclase stimulators. This work highlights a direct link between globin‐mediated nitric oxide metabolism and organ laterality. Foundational research in mammalian systems established cytoglobin as a major nitric oxide dioxygenase within vascular smooth muscle, controlling nitric oxide decay, vascular relaxation and blood pressure. Genetic ablation prolongs nitric oxide half‐life, enhances vasorelaxation and confers protection against hypertensive stimuli. Together, these studies underscore cytoglobin’s dual role in developmental morphogenesis and cardiovascular regulation through oxygen‐dependent modulation of nitric oxide bioavailability.

Globin Proteins in Neurophysiological Contexts publication trend

The graph below shows the total number of articles in globin proteins in neurophysiological contexts across all publications each year (not limited to Nature Index journals).

Technical terms

Globin: A family of heme‐binding proteins historically linked to oxygen transport and storage, now known to mediate gas signalling and redox chemistry.

Neuroglobin: A hexacoordinate globin expressed in neurons and glia, implicated in oxygen homeostasis, redox regulation and neuroprotection.

Cytoglobin: A ubiquitously expressed hexacoordinate globin that regulates nitric oxide metabolism, redox signalling and vascular function.

Androglobin: A multi‐domain globin featuring a circularly permuted globin module, involved in nitric oxide homeostasis and cellular signalling beyond classical haemoglobin roles.

Hexacoordination: A binding mode in which the heme iron is coordinated by six ligands, typically including a distal histidine, affecting ligand affinity and kinetics.

Soluble guanylate cyclase (sGC): An enzyme activated by nitric oxide that generates cyclic GMP, a second messenger in vascular and neural signalling.

References

1. Cytoglobin regulates NO-dependent cilia motility and organ laterality during development. Nature Communications (2023).
2. The circularly permuted globin domain of androglobin exhibits atypical heme stabilization and nitric oxide interaction. Chemical Science (2024).
3. Insights into the function of cytoglobin. Biochemical Society Transactions (2023).
4. Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall. Nature Communications (2017).
5. Protection by Neuroglobin Expression in Brain Pathologies. Frontiers in Neurology (2016).