CDNF: What It Is and How To Increase Cerebral Dopamine Neurotrophic Factor

Cerebral Dopamine Neurotrophic Factor

 
 

Cerebral Dopamine Neurotropic Factor (CDNF) is a newly discovered (and very powerful) way to regrow damaged dopaminergic neurons. R

It has shown to have anti-inflammatory effects that are very beneficial in models of Parkinson's Disease. R

Contents:

  1. Basics
  2. Benefits
  3. How To Increase CDNF
  4. Mechanism of Action
  5. Genetics
  6. More Research

Basics

Cerebral Dopamine Neurotropic Factor (like BDNFNGFCNTF, and GDNF, and MANF) is a protein that increases neurogenesis (growth of neurons) in the brain. R

CDNF was found after the discovery of Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF), another dopamine protection protein. R

Areas of the brain CDNF is expressed in:

  • Brain Stem R
  • Cerebellum R
  • Cerebral Cortex R
  • Hippocampus R
  • Hypothalamus R
  • Locus Coeruleus R
  • Striatum R
  • Substantia Nigra R
  • Thalamus R

Benefits

1. Heals Parkinson's Disease

CDNF (as well as GDNF and MANF) is commonly low in Parkinson's Disease (PD) patients. R R

Parkinson's Disease (PD) is characterized by a loss of dopaminergic (DAergic) neurons in the substantia nigra (SN) as well as an accumulation of α-synuclein (a biomarker of PD) in the central and enteric nervous system. R

CDNF is able to restore dopamine and the function of brain lesions of PD models in vivo. R R

This effect is even greater when combined with GDNF or MANFR R

CDNF can dissolve α-synuclein buildup in neurons. R R

It can decrease the damage of dopamine neurons from oxidopamine (6-OHDA). R R

It can decrease damage from MPTP (a neurotoxic precursor for dopamine neurons). R

CDNF also improves motor functions in animal models of PD. R R

2. Protects and Heals The Brain

 
 

CDNF protects against neuroinflammation. R

CDNF decreases overall stress to the cells. R

CDNF can regenerate the dopamine cells in the brain by suppressing neuroinflammation of astrocytes and microglial cells. R

CDNF can protect dopamine neurons from stroke-induced damage. R

3. Protects Brain Against Toxins

CDNF protects dopamine cells against toxin induced damage. R

CDNF injected into rat brains can protect the brain against amphetamine-induced damage. R

It can also protect against methamphetamine (METH) neurotoxicity. R

4. Helps With Memory

CDNF-therapy can improve long-term memory in mice. R

For example, in PD, CDNF can increase cognitive function. R 

Also CDNF has shown to be helpful for cognition and long term memory in models of Alzheimer's Disease (AD) when injected into the hippocampus (memory center of the brain). R R

In early stage AD, CDNF reduces amyloid-beta-induced toxicity to brain cells. R

5. Helps With Nerve Injury

 
 

Peripheral nerve injury (PNI) can result in axonal degeneration and loss of neurons, which leads to limited nerve regeneration and severe functional impairment. R

CDNF improves axonal and Schwann cell regeneration and increases the thickness of the myelination around the axons. R

For example, stem cells that were given CDNF before injury had an even greater effect at increasing myelination thickness, axon diameter and axon-to-fiber diameter ratio. R

6. Protects The Heart

When CDNF was injected into heart cells, it protected them against the toxic effects of tunicamycin (TM). R

How To Increase CDNF

I will be updating this list as new research become available. 

Drugs:

  • Selegiline (slightly) R
  • Valproic Acid R R R

Pathways:

  • Inhibiting Sar1 (possibly) R
  • Increasing T-regs - upregulates CDNF (and TGFB1) R

Other:

  • Arsenic (Sodium arsenate) R
  • CDNF-expressing bone marrow-derived mesenchymal stem cells (MSCs) R
  • CDNF-expressing bone marrow-stromal cells (BMSCs) R
  • CDNF Protein or Viral Bound - (dose dependent) R R
  • Decabromobiphenyl Ether R
  • Propionaldehyde R
  • Malaria R

What Decreases CDNF?

Mechanism Of Action

CDNF is also called ARMET-like protein 1 or conserved dopamine NTF. R

Simple:

  • CDNF works on increasing tyrosine hydroxylase neurons and restoring dopamine's function in lesions. 
  • It has only shown to be beneficial when neurons are damaged.

Advanced:

  • CDNF has no effects on naive, healthy cells and neurons, and it requires a lesion for its action. R
  • For example, CDNF and MANF seem not to affect un-lesioned, healthy neurons in vitro and in vivo, but efficiently protect and repair lesioned DA neurons. R R
  • CDNF and GDNF have an additive effect in restoring dopaminergic (DAergic) function and number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) of 6-hydroxydopamine (6-OHDA)-lesioned rats. R R
  • Together they activate the pERK1/pERK2 pathway. R
  • CDNF (as well as GDNF) help Unfolded Protein Response (UPR) homeostasis in the endoplasmic reticulum (ER), which helix-7 in the C-terminal is important for CDNF secretion. R R R
  • CDNF and MANF (unlike GDNF) may stay in the ER after translation. R
  • CDNF exerts its trophic effect by regulating the ER stress response since CDNF decreases the phosphorylation of eIF2α. R
  • It decreases ATF6, GRP78 and eIF2alpha in the ER. R
  • MPTP can cause Parkinsonian symptoms in humans and CDNF can not only restore the DAergic circuitry but also protect cell bodies. R R
  • CDNF increases dopamine transporter (DAT) and TH neurons in the SN and striatum. R
  • CDNF administration or overexpression reduces the LPS-induced cytotoxicity, astrocyte ER stress-induced cellular damage, and the production of proinflammatory cytokines via inhibiting the JNK signaling pathway, decreasing PGE2, IL-1β, IL-6 and TNF-α. R R R R R
  • In AD, CDNF reduces the expression levels of ER stress-related proteins, including Bip (also known as GRP78), phosphorylation of eukaryotic translation initiation factor 2 subunit α (peIF2α), phosphorylation of c-Jun N-terminal kinase (pJNK), and cleaves caspase 3. R
  • CDNF blocks apoptosis via interacting with Bax-associated pathways. R R
  • The tissue half-life of infused recombinant human CDNF (rhCDNF) in the striatum is 5.5 h and is undetectable in the SN after 2 days, but will stay around longer if there is damage to the tissue. R

Genetics

CDNF is encoded by the CDNF gene.

  • rs7094179 - C allele has increased risk for PD R
  • rs1901650 
  • rs11259365
  • rs2278871
  • rs11818228
  • rs7900873
  • rs7099185
  • rs11814733
  • rs6602768
  • rs3588973
  • rs35258308

CDNF (rs11259365, rs7094179, rs7900873, rs2278871) is probably unrelated to cocaine dependence. R

More Research

  • CDNF given in a viral form can inhibit the formation in hypothalamic neurons in animal models of PD. R
  • CDNF is slightly more effective than VEGF-B in protecting DA neurons. R
  • Clinical Trials (updated 2017) R R R R