Persephin Explained

Persephin is a neurotrophic factor in the glial cell line-derived neurotrophic factor (GDNF) family. Persephin shares around a 40% similarity in amino acid sequence compared to GDNF and neurturin, two members of the GDNF family.[1]

Function

Persephin has been found to be less potent than other members of the GDNF family. It has been found to support the survival and morphological differentiation of tyrosine hydroxylase immunoreactive neurons, although less so than both GDNF and neurturin.[2] The mRNA levels of persephin in developing neurons has been low compared to other neurotrophic factors, but relatively higher levels of persephin mRNA have been found in embryonic neurons.

Similarly to the other members of the GDNF family of ligands, persephin uses a receptor that consists of the tyrosine kinase signaling component Ret and a unit of glycosylphosphatidylinsitol (GPI)-anchored receptor (GFRα). Persephin specifically binds to GFRα4.[3]

Persephin acts on both neurons in the CNS and PNS, but also has the ability to act as a renal ramogen.

Structure

Unlike other GDNF family of ligands, persephin only contains one RXXR cleavage site, rather than multiple, indicating that it can only make one length of functional peptide.

Therapeutics

Persephin has the potential to be used as a therapeutic treatment for neurodegenerative diseases, such as Parkinson's disease and other diseases that affect motor neurons. Because persephin acts more selectively compared to other GFLs, such as GDNF, it may produce fewer mechanism-based complications, making it a stronger therapeutic target.

Notes and References

  1. Milbrandt J, de Sauvage FJ, Fahrner TJ, Baloh RH, Leitner ML, Tansey MG, Lampe PA, Heuckeroth RO, Kotzbauer PT, Simburger KS, Golden JP, Davies JA, Vejsada R, Kato AC, Hynes M, Sherman D, Nishimura M, Wang LC, Vandlen R, Moffat B, Klein RD, Poulsen K, Gray C, Garces A, Johnson EM . 6 . Persephin, a novel neurotrophic factor related to GDNF and neurturin . Neuron . 20 . 2 . 245–53 . February 1998 . 9491986 . 10.1016/s0896-6273(00)80453-5 . 10943214 . free .
  2. Zihlmann KB, Ducray AD, Schaller B, Huber AW, Krebs SH, Andres RH, Seiler RW, Meyer M, Widmer HR . 6 . The GDNF family members neurturin, artemin and persephin promote the morphological differentiation of cultured ventral mesencephalic dopaminergic neurons . Brain Research Bulletin . 68 . 1–2 . 42–53 . December 2005 . 16325003 . 10.1016/j.brainresbull.2004.10.012 . 31594656 .
  3. Andres R, Forgie A, Wyatt S, Chen Q, de Sauvage FJ, Davies AM . Multiple effects of artemin on sympathetic neurone generation, survival and growth . Development . 128 . 19 . 3685–95 . October 2001 . 10.1242/dev.128.19.3685 . 11585795 .