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

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

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?

• Arsenic (Arsenic trioxide) R
• AZM551248 R
• Benzo[a]pyrene R
• BPA R
• Caffeine R
• Carbamazepine R
• Dibenzothiophene R
• Silicone R
• Spaceflight R R
• Tretinoin R

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

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

• 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