persephin

Persephin, also known as PSPN, is a secreted member of the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs). This family includes GDNF, neurturin, artemin, and persephin, all of which are growth factors that support neuronal survival and development. Persephin is produced as a precursor protein that is cleaved to a mature, secreted form and shares the characteristic cystine-knot motif of GFLs.

Receptors and signaling pathways for persephin involve binding to the GFRα4 co-receptor, in complex with the RET receptor tyrosine kinase. Activation of RET initiates intracellular signaling cascades such as the MAPK/ERK and PI3K/AKT pathways, promoting neuronal survival, differentiation, and neurite outgrowth in responsive cell populations. The signaling effects of persephin tend to be more restricted in scope compared with some other GFLs, consistent with its more specific pattern of activity.

Expression and function vary by species and developmental stage. Persephin is detected in the developing nervous system and in certain adult neural tissues, with distribution that appears more restricted than other GFL members. Its precise physiological roles are still being studied, but it is implicated in motor neuron development and maintenance, and may influence aspects of dopaminergic or sensory neuron biology in some contexts.

Research and clinical status remain exploratory. In preclinical models, persephin can support motor neuron survival and axon growth, yet it is generally less potent than GDNF. There are no approved therapies based on persephin alone, though understanding its biology contributes to broader insight into GFL signaling and potential combinatorial neurotrophic strategies.

See also: GDNF family ligands, GFRα receptors, RET.