P21
preclinicalAlso known as: P021
**Mechanism of Action** P21 (P021) is a synthetic peptide derived from ciliary neurotrophic factor (CNTF) that acts as a small-molecule mimetic of CNTF's neuroprotective signaling. It selectively activates the CNTF receptor complex (CNTFRα, gp130, and LIFRβ), leading to downstream JAK/STAT3 and MAPK/ERK pathway activation. This signaling cascade promotes neural stem cell proliferation and differentiation, particularly in the hippocampus, while simultaneously reducing tau hyperphosphorylation and aggregation through modulation of glycogen synthase kinase-3β (GSK-3β) activity. The peptide does not cross the blood-brain barrier efficiently, but systemic administration has shown central effects, likely via peripheral signaling or circumventricular organ interactions. **Key Research Findings** Preclinical studies in transgenic Alzheimer's disease (AD) mouse models (e.g., 3xTg-AD) demonstrate that chronic P21 treatment enhances hippocampal neurogenesis, improves spatial memory in Morris water maze tests, and reduces soluble and insoluble tau pathology by 30–50%. The peptide also decreases neuroinflammation markers (e.g., IL-6, TNF-α) and restores synaptic plasticity markers (e.g., PSD-95, synaptophysin). Notably, P21 does not significantly alter amyloid-β plaque burden, suggesting its effects are tau-centric and neurogenic rather than amyloid-directed. No overt toxicity has been reported in rodent studies. **Clinical Relevance** P21 remains in preclinical development, with no human trials initiated to date. Its dual action—promoting neurogenesis and targeting tau pathology—positions it as a potential disease-modifying candidate for AD and other tauopathies. However, challenges include optimizing bioavailability and confirming target engagement in humans. The peptide's CNTF-derived mechanism may also carry risks of weight loss or immune modulation, as seen with full-length CNTF. For research purposes only — not medical advice.
Key data
C27H42N6O8Research & studies
Cytoplasmic p21 increased spheroid formation and CD133 expression in a mechanism partly dependent on AKT activation.; Phosphomimetic p21 (T145D) enhanced stemness factors (Oct3/4, Nanog, Sox2), while nuclear p21 (T145A) reduced them.; Cytoplasmic p21 interacts with the NF-κB-IκB complex, promoting NF-κB activation and upregulation of BCL-xL and COX2.; Screening p21 subcellular localization may stratify CRC patients with high metastatic risk for CSC-targeted therapies.
p21-mNeonGreen expression correlates with indel frequencies, useful for gRNA screening.; Double-stranded ODNs and AAVs trigger stronger p21 activation than single-stranded forms.; Lentiviral vectors induce lower p21 expression than AAVs, making them preferable for sensitive cells.; Viral promoter selection, such as SFFV, significantly affects p21 activation levels.
Loss of p21 increases trabecular bone formation post-injury.; Loss of E2f1 increases cortical bone formation but leads to poorer bone repair overall.; E2f1 absence dramatically decreases osteoblasts, osteoclasts, and chondrocytes at the injury site.; E2f1 and p21 have distinct roles in bone regeneration, with E2f1 regulating cell populations required for repair.
p21 knockout reduced senescent cell presence and alleviated chronic lung inflammation pathology in mice.; p21 knockout improved the fitness of mice subjected to chronic LPS exposure.; Resident epithelial and endothelial cells, not immune cells, mediate p21-dependent inflammatory responses.; p21 is implicated as a critical regulator and driver of chronic airway inflammation and lung destruction.
p53 promoter-based reporter gene expression depends on p21 levels and requires p53/p21 interaction.; Puma expression is p53-dependent regardless of irradiation, while Mdm2 and Gadd45a expression is p53-dependent only in irradiated cells.; p53/p21 interaction is required for p53-dependent expression of tested genes, but not for Mdm2 and Gadd45a in non-irradiated cells.; p21 is required for p53 binding to the promoters of Puma, Mdm2, and Gadd45a.
Frequently asked questions
What is P21?
**Mechanism of Action** P21 (P021) is a synthetic peptide derived from ciliary neurotrophic factor (CNTF) that acts as a small-molecule mimetic of CNTF's neuroprotective signaling. It selectively activates the CNTF receptor complex (CNTFRα, gp130, and LIFRβ), leading to downstream JAK/STAT3 and MAPK/ERK pathway activat
How does P21 work?
CNTF-derived peptidergic compound that promotes neurogenesis and reduces tau pathology in preclinical Alzheimer's models.
What is the research status of P21?
P21 is currently classified as preclinical, with 41,238 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of P21?
P21 has a molecular weight of approximately 578.7 g/mol (formula C27H42N6O8).
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