Persephin (PSPN)

Persephin is a secreted neurotrophic factor belonging to the glial cell line-derived neurotrophic factor (GDNF) family, itself part of the TGF-beta superfamily[4][1][2][3]. It acts primarily by promoting survival and morphological differentiation of motor neurons and midbrain dopaminergic neurons, with additional roles in kidney development as a renal ramogen[1][2][4][3]. Persephin achieves its biological effects by binding to the GFRα4 coreceptor, which activates the RET tyrosine kinase signaling receptor, leading to downstream signaling that promotes neuronal survival, growth, and function[4][2][3]. Its selectivity and mechanism have attracted interest as a potential therapy in neurodegenerative diseases, notably Parkinson’s and Alzheimer’s disease, and it is upregulated in some cancers, especially oral squamous cell carcinoma[2][1][4]. While demonstrating promise in preclinical studies, persephin’s therapeutic applications in humans remain experimental, with its mechanism and safety profile still under investigation[1][3].

Other names

PersephinPSPNPSPpersephin

Promotion of neuronal survival through activation of the RET receptor tyrosine kinase via coreceptor GFRα4 (in humans) or occasionally GFRα1 Potential engagement of downstream MAPK (mitogen-activated protein kinase) pathways