P21 is a peptide that was developed by reverse engineering Cerebrolysin’s effect using epitope mapping. Researchers found that the main neurogenic and memory enhancing effects from Cerebrolysin were due to its ability to react to human CNTF [ciliary neurotrophic factor].
when P21 was first synthesized in 2010, it was discovered that it could “improve learning and memory, promote neurogenesis and synaptic plasticity in mice. Let’s delve into its benefits:
P-21 peptide has shown promising effects on brain health.
Autistic Neurodegeneration:
- P-21 has been found to reverse neurodegeneration associated with autism.
- It improves cognition, memory, and reasoning by promoting the formation of new neurons in the brain1.
- Specifically, it rescues structural abnormalities caused by autistic sera and reduces oxidative stress1.
Alzheimer’s Disease and Neuroprotection:
- P-21 slows the progression of neurodegeneration and Alzheimer’s disease.
- It achieves this by:
- Removing Tau protein build-up.
- Reducing the production of Beta Amyloid plaques2.
Enhanced Neuroplasticity:
- P-21 may enhance neuroplasticity, which refers to the brain’s ability to reorganize itself.
- This can lead to improved cognitive function and memory3.
In summary, P-21 holds promise as a neuroprotective and cognition-enhancing peptide.
So the researchers narrowed their search, and found that an 11-mer peptide, labeled peptide 6 (Ac-VGDGGLFEKKL-NH2), enhanced hippocampus-dependent learning and memory, increased neurogenesis, and neuronal plasticity.
They then determined the most active sub-sequence in the peptide called peptide 6C (Ac-DGGL-NH2). However, this peptide sequence showed to have poor blood brain barrier permeability, and was easily broken down by plasma enzymes.
To combat this, they added an adamantane moiety to the N-terminus of the peptide sequence. This highly lipophilic tricyclic alkane greatly increased the BBB permeability, and protected the peptide from enzymatic degredation.
This made the new peptide able to be active when taken via subcutaneous administration. That is how P21 (Ac-DGGL^A-NH2) was born
P21 has been explored for its potential anti-inflammatory effects.
In animal studies, P21 has been shown to inhibit the growth of cancer cells and induce cell death 1.
Peptide P21 is also a cell cycle inhibitor that is involved in essential cellular processes such as cell cycle arrest, apoptosis, and transcriptional regulation, as well as differentiation, senescence, and DNA repair
Peptide P21 has also been shown to reverse autistic neurodegeneration while improving cognition, memory, and reasoning through new neuron formation in the brain.
Peptide P21 has shown to slows the progression of neurodegeneration and Alzheimer’s by removing Tau protein build-up and reducing the production of Beta Amyloid plaques.
Moreover, the P021 treatment markedly reduced tau pathology and attenuated the generation but not the clearance of Aβ in 3xTg-AD mice.”
Cognitive performance was studied by assessing episodic memory with Novel Object Recognition task at 16-17-months post-treatment. We found that P021 treatment initiated during the synaptic compensation period can prevent neurodegeneration, Aβ and tau pathologies, rescue episodic memory impairment, and markedly reduce mortality rate. These findings for the first time show effective prevention of AD changes with a neurotrophic compound that targets neurogenesis and synaptic plasticity, suggesting that improving the health of the neuronal network can prevent AD.”
“The AD brain responds to neurodegeneration by stimulating neurogenesis, however, because of the lack of a proper neurotrophic microenvironment of the hippocampus, this effort of the AD brain to replace lost neurons with new neurons is unsuccessful and culminates in failure of neuronal survival, maturation, and integration. As the disease progresses, the neurogenic failure becomes severe, and contributes significantly to cognitive decline
