PE-22-28

PE-22-28 is a spadin-derived peptide that blocks TREK-1 potassium channels implicated in mood and cognition. It shows rapid antidepressant effects, increases neurogenesis within days, and supports synaptic plasticity with fewer side effects than traditional antidepressants.

- Support mood regulation and reduce anxiety/depression

- Enhance cognition and neuroprotection

Mechanism of Action

How this peptide works in the body

PE-22-28 blocks TREK-1 potassium channels, reducing potassium (K⁺) efflux from neurons, which stabilizes membrane potential and increases neuronal excitability. This enhances resistance to stress-induced dysfunction by preventing excessive neuronal hyperpolarization.

Neurogenesis:

PE-22-28 promotes the proliferation and differentiation of neural progenitor cells in the hippocampus by upregulating brain-derived neurotrophic factor (BDNF) and activating the Wnt/β-catenin signaling pathway. This supports neural regeneration and cognitive enhancement.

Synaptic Plasticity:

PE-22-28 enhances dendritic spine density and modulates NMDA receptor activity, improving synaptic strength and learning capacity. It also increases calcium (Ca²⁺) influx via NMDA receptor trafficking, reinforcing long-term potentiation (LTP) and memory formation.

Mood Stabilization:

PE-22-28 regulates serotonin (5-HT) and dopamine (DA) neurotransmission by modulating monoaminergic pathways influenced by TREK-1 inhibition. This contributes to rapid antidepressant effects without the side effects of traditional antidepressants.

Inflammation Modulation:

PE-22-28 reduces neuroinflammation by suppressing pro-inflammatory cytokines (IL-6, TNF-α) and mitigating oxidative stress. This protects neurons from inflammatory damage and supports overall brain health.

PE-22-28 reduces neuroinflammation by suppressing pro-inflammatory cytokines (IL-6, TNF-α) and mitigating oxidative stress. This protects neurons from inflammatory damage and supports overall brain health.