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P21 (also known as P021 or Ac-DGGLAG-NH2) is a synthetic peptidomimetic compound.
• Origin: Derived from a small 4-amino-acid active region of human ciliary neurotrophic factor (CNTF) with an attached adamantane group.
• Blood-Brain Barrier: The adamantane addition makes the molecule lipophilic (fat-soluble), allowing it to cross the blood-brain barrier.
• Distinction: It is completely different from the endogenous natural cell-cycle regulator protein known as p21 (CDKN1A).
Proposed Mechanism of Action (Preclinical)
• BDNF Upregulation: Stimulates brain-derived neurotrophic factor (BDNF) expression and activates downstream TrkB-PI3K-Akt signaling pathways.
• LIF Inhibition: Competitively inhibits the leukemia inhibitory factor (LIF) pathway.
• Tau/Neurogenesis: Studied in animal models for promoting hippocampal neurogenesis, synaptic plasticity, and reducing tau hyperphosphorylation (linked to Alzheimer's disease models).
• Preclinical Only: Research on P21 is strictly limited to laboratory, cellular, and animal models.