Glial cell-derived neurotrophic factor (GDNF) (GDNF)

Glial cell-derived neurotrophic factor (GDNF) is a potent survival factor for several neuronal populations, most notably the midbrain dopaminergic neurons that degenerate in Parkinson's disease. A member of the TGF-beta superfamily, GDNF is synthesized as a precursor protein and secreted as a glycosylated, disulfide-bonded homodimer that signals through the RET receptor tyrosine kinase and its co-receptor GFRA1 [2, 4, 13]. Beyond its neuroprotective role, it is essential for the development of the enteric nervous system, kidney morphogenesis (ureteric branching), and the maintenance of spermatogenesis [2, 13]. In therapeutic development, GDNF has been targeted primarily through intracranial infusion of recombinant protein or gene therapy using viral vectors like AAV2 to bypass the blood-brain barrier [1, 8, 12, 15]. While GDNF has demonstrated remarkable restorative effects in animal models of neurodegeneration, clinical success in humans has been complicated by delivery obstacles and the need for precise localization within the brain [6, 8, 12]. Ongoing research continues to explore its potential in disease modification and as a biomarker for neurodegenerative and psychiatric disorders [19, 20].

Other names

Astrocyte-derived trophic factorATF1ATF2HFB1HSCR3

GDNF binds to the Glial cell line-derived neurotrophic factor receptor alpha-1 (GFRA1) co-receptor, which then recruits and activates the RET receptor tyrosine kinase, initiating downstream signaling through the MAPK/ERK and PI3K/Akt pathways to promote neuronal survival and repair.