Persephin is a

neurotrophic factor Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and cell differentiation, differentiation of both developing and mature neurons. Most ...

in the

glial cell line-derived neurotrophic factor Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particula ...

(GDNF) family. Persephin shares around a 40% similarity in amino acid sequence compared to GDNF and neurturin, two members of the GDNF family.

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 Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particula ...

and

neurturin Neurturin (NRTN) is a protein that is encoded in humans by the ''NRTN'' gene. Neurturin belongs to the glial cell line-derived neurotrophic factor (GDNF) family of neurotrophic factors, which regulate the survival and function of neurons. Neur ...

. 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 The GDNF family of ligands (GFL) consists of four neurotrophic factors: glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN), and persephin (PSPN). GFLs have been shown to play a role in a number of biological process ...

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

Structure

Unlike other

, 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 Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

and other diseases that affect

motor neurons A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly ...

. Because persephin acts more selectively compared to other GFLs, such as

, it may produce fewer mechanism-based complications, making it a stronger therapeutic target.

References

External links

* TGFβ domain Neurotrophic factors {{biochem-stub