GDNF: What It Is and 34+ Ways To Increase Glial Cell Line-Derived Neurotrophic Factor

Glial Cell Line-Derived Neurotrophic Factor

Glial cell line-derived neurotrophic factor (GDNF) is an essential growth factor for the kidneys, spinal cord, exerting a wide range of effects on addiction, Alzheimer's, Parkinson's, neuropathy, gut inflammation, and more. R



GDNF was discovered in 1991 by researchers at Syngeren in Boulder, Colorado. R

GDNF is a protein (like BDNF, NGF, and CNTF). R

It promotes the survival of many neuron types. R

It may contribute to learning and memory. R

GDNF also regulates kidney development and spermatogenesis, and it affects alcohol consumption. R


1. Improves Parkinson's Disease


GDNF is known to be down-regulated in Parkinson's disease patients. R R

GDNF has regenerative properties for brain cells and shows may be potential treatment for PD. R

Monkeys with PD showed less trembling with taking GDNF. R

In humans, neuronal fibers grew in part of the brain that were exposed to GDNF. R

Animal models of PD have shown that several neurotrophic factors, including GDNF and other compounds, reduce apoptosis and increase resistance of dopamine neurons to neurotoxins in vitro. R

2. Helps Alcoholism


GDNF reduces the motivation to consume and seek alcohol (via activation of the MAPK pathway). R

It does this by inhibiting the need to binge drinking. R

3. Plays A Role in Kidney Development

GDNF helps the kidneys develop by promoting the branching of the ureteric bud. R

Kidneys that developed without the GDNFr gene, displayed significant branching abnormalities. R

4. Helps Peripheral Nervous System Functions


GDNF regulates neurite branching, synaptic plasticity, and phenotypes of several neuronal populations. R

It promoted differentiation of:

  • Kidney R
  • Lung R
  • Pancreas R
  • Germ cells R
  • Myocytes
  • Thymocytes R

5. May Help Treat Addiction


Reduced levels of endogenous GDNF created changes in (dorsal striatal and accumbal) dopaminergic transmission. R

Endogenous GDNF may regulate dopamine in treating addiction. R

For example, repeated morphine administration increases GDNF expression (by stimulating VTA dopaminergic neurons). R

Another example, GDNF helped rats crave less cocaine. R R

Essentially, rats that expressed less GDNF or had lower levels craved more stimulants and opioids. R R

6. Plays a Role in ALS and Alzheimer's Disease


GDNF has been shown to be dysregulated in in Alzheimer's patients' brains. R

In Alzheimer's patients, GDNF was higher in CSF and plasma, but decreased serum concentration. R R

Also, GDNF administration can protect against Alzheimer's from aluminum. R

7. Supports Neuronal Health


NGF, GDNF, and GFLs are crucial for the development and maintenance of distinct sets of central and peripheral neurons. R

Exogenous GDNF supports survival of:

  • noradrenergic neurons R
  • spinal motor neurons R R
  • peripheral sensory and autonomic neurons R 
  • forebrain cholinergic and GABAergic neurons R 

8. Protects the Brain

 GDNF protected the brain from stroke (by blocking the increase of NO during stroke). R

GDNF injected two days before a full artery blockage prevented the loss of hippocampal neurons. R

9. Helps Neuropathy


Neuropathic pain arises as a debilitating consequence of nerve injury. R

GDNF both prevented and reversed sensory abnormalities that developed in neuropathic pain. R

GDNF may be a therapeutic treatment for neuropathic pain. R

10. Plays A Role in the Pancreas

Exogenous GDNF supports the survival of pancreatic  β-cells. R

Over expression of GDNF may be a sign for pancreatic cancer. GDNf may also be important for pancreatic cancer development. R

It does this by upregulating the expression and enzymatic activity of MMP-9. R

So it's probably better to not try to increase GDNF if you have pancreatic cancer. 

11. May Be Useful After LCSD


Left cardiac sympathetic denervation (LCSD) is an important therapeutic option for patints with (LQTS) long QT syndrome and (CPVT) catecholaminergic polymorphic ventricular tachycardia. R

In rats, GDNF was produced for nerve regeneration. This may be helpful for patients recovery after LCSD. R

12. Important for the Gut

Chronic inflammatory bowel disease (IBD) is most commonly categorized into Crohn's disease (CD) and ulcerative colitis (UC) and afflicts primarily the distal small and large intestine. R

In patients with CD, GDNF was increased. Reducing GDNF in the gut may help patients with CD. R

GDNF enhances the migration of colon cancer cells (by increasing VEGF-VEGFR interaction). R

In early stage gastric cancer, GDNF (along with MINT25) were molecular markers for the disease. R

13. May Improve Auditory Perception


GDNF along with chronic electrical stimulation in cochlear implant recipients may improve their auditory perception. R

14. May Help the Testes

Sertoli cells are in the testicles responsible for producing sperm and testes formation. R R R 

GDNF stimulates the proliferation of immature Sertoli cells (by activation of ERK1/2 signaling pathway). R

15. May Help with Mood Disorders


Lower GDNF levels might be involved in the pathophysiology of mood disorders. R R

GDNF may be lower in patients with major depression and bipolar disorder. R


How To Increase GDNF



  • Calorie Restriction R
  • Exercise R
  • Intermittent Fasting R
  • Royal Jelly R
  • Stress Reduction (GDNF is suppressed by stress) R




  • Anti-depressants R
  • Ibogaine R 
  • M30 R
  • Noribogaine R 
  • Pulichalconoid B R
  • Selegiline R
  • Telmisartan R


  • Electroconvulsive Therapy R
  • Electro Acupuncture R
  • Increasing TNF-alpha (without raising IL-1b or IL-6) R
  • Radiation Therapy R
  • Semen R

Decrease GDNF

Mechanism of Action


GDNF, together with three related molecules, neurturin, artemin, and persephin, constitutes the GDNF family ligands. R

The neurotrophic effect of GDNF, except in motoneurons, requires the presence of TGF- β, which activates the transport of GFRα1 to the cell membrane. R R

It recruits either RET or NCAM for intracellular signaling. R


  • Upregulates B cell lymphoma 2 (BCL2) R
  • Upregulates heat shock 60 kDa protein 1 (HSP60) levels R
  • Suppresses LDH leakage R
  • Promotes MMP R



This gene encodes a secreted ligand of the TGF-beta superfamily of proteins. R

Mutations in this gene may be associated with Hirschsprung's disease. R 

No single SNP could be identified as being the causal one. R


  • rs142426358
  • rs2075680
  • rs6330
  • rs121918535
  • rs79853121
  • rs11242417
  • rs2506030
  • rs104893891
  • rs36119840
    • Mutations may be associated with Tourette syndrome. R
  • rs10461985

More Research

  • High doses of GDNF inhibited REM sleep in rabbits. R
  • Human T cells, B cells, and monocytes produce NTN but not GDNF. R
  • GDNF and Forskolin targeted different subpopulations of TH/TFF1 neurons. R
  • Administration of GDNF improved saliva production. R
  • GDNF-RET signaling promoted the survival of aromatase inhibitor-resistant cells and elicited resistance in aromatase inhibitor-sensitive cells, during treatment of breast cancer. R