DNSP-11

Also known as: Dopamine Neuron Stimulating Peptide-11

Overview

DNSP-11 is a synthetic peptide derived from a segment of the GDNF proprotein, studied for its potential to support dopamine production and protect neurons from damage. Early research indicates its ability to enhance dopamine turnover and promote neuroplasticity in animal models. DNSP-11 is an 11-amino acid peptide believed to be cleaved from the pro-region of GDNF. In vivo studies suggest it enhances dopamine turnover and triggers ERK1/2 phosphorylation, promoting neuronal survival and synaptic plasticity.

Benefits

- Enhances dopamine turnover without increasing baseline release

- May improve recovery in Parkinsonian models

- Promotes neuronal growth and survival

- Activates ERK1/2 neuroprotective signaling

Consider This Peptide If You Want To

- Researching neuroprotective or dopaminergic therapies

- Investigating compounds that support dopamine turnover and neuronal function

Dosage & Administration

Dosage Guidelines

Recommended Dosage

• Amount:200 mcg

• Frequency:daily

• Duration:3 weeks

• Rest Period:

• Time of Day:morning

• Ingestion:intranasal

Dosage varies significantly between species. Currently only researched in animal models, primarily using intranasal or intracerebral delivery methods.

Administration Routes:Intranasal DeliveryIntracerebral Delivery

Research Findings on Dosage:

Intranasal or Intracerebral Delivery (animal studies): ● Commonly Reported Dosage: 200–300 mcg/day in rats; higher escalation from 0.3 to 10 mg/day in nonhuman primates ● Duration: Typically administered daily over 3 to 10 weeks

Mechanism of Action

How this peptide works in the body

ERK1/2 Pathway Activation: ● DNSP-11 stimulates phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which regulate cell survival, synaptic plasticity, and long-term potentiation. ERK1/2 activation enhances neurotrophic signaling through Ras/Raf/MEK pathways, supporting dopamine neuron maintenance. Modulation of Dopamine Turnover: ● DNSP-11 increases dopamine turnover in specific regions of the striatum without affecting baseline dopamine levels. This may be due to changes in vesicular monoamine transporter-2 (VMAT2) function and dopamine transporter (DAT) reuptake efficiency, promoting enhanced dopaminergic neurotransmission under stimulated conditions. Synaptogenesis and Neurite Outgrowth: ● DNSP-11 is believed to support neuronal growth cone formation and promote axonal regeneration by upregulating intracellular effectors such as GAP-43 and cytoskeletal remodeling proteins. These actions may facilitate synapse formation and repair in damaged dopaminergic circuits. Anti-Apoptotic and Mitochondrial Effects: ● DNSP-11 has shown protective activity against neuronal apoptosis by inhibiting caspase-3 activation and stabilizing mitochondrial membrane potential. This contributes to its neuroprotective role, particularly in oxidative stress or 6-OHDA-lesioned models. Glial Modulation: ● There is preliminary evidence that DNSP-11 may influence glial-neuronal interactions, potentially through astrocyte-secreted growth factors or modulation of neuroinflammatory cytokines, further enhancing the neuroprotective environment.

Consider Stacking With

- Cerebrolysin or BDNF-stimulating peptides

- Mitochondrial support agents (e.g., SS-31)

Side Effects & Cautions

Common Side Effects

- None reported in rodent or primate studies (long-term unknown)

Cautions

- Requires further investigation for dosing safety and toxicity

Research & References

Research Highlights

● Increased potassium-evoked dopamine release in the striatum after DNSP-11 administration ● ERK1/2 phosphorylation in MN9D dopaminergic cell lines, suggesting synaptic plasticity enhancement ● Maintains neuroactivity in 6-OHDA Parkinson's rat models

References

Fuqua JL, et al. "Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro." Peptides. 2014;54:90–98. doi:10.1016/j.peptides.2013.12.007.

Cass WA, et al. "Neurochemical and behavioral effects of DNSP-11, a novel peptide derived from the prosequence of GDNF." Exp Neurol. 2008;212(1):244–256.

Bradley LH, et al. "Biological activity of DNSP-11 in vitro and in vivo in models of dopaminergic neuron function." J Neurosci Res. 2011;89(10):1626–1634.