P21 (WAF1, CIP1, or SD11)

Introduction

P21 is a nootropic peptide targeting improved neurogenesis. In animal studies, P21 has been shown to boost levels of BDNF (brain-derived neurotrophic factor), thus promoting neurogenesis (nerve growth) and inhibiting the formation of Amyloid plaques and Tau proteins seen in Alzheimer's disease. BDNF has been linked not just to enhanced neurogenesis, but to the down regulation of certain enzyme responsible for tau and amyloid plaque formation in Alzheimer's brains. P21 has been shown to improve cognition in animal models.

It works by inhibiting something that inhibits neurogenesis in the dentate gyrus. The factor that inhibits neurogenesis is called Leukaemia inhibiting factor (LIF). P021 does not bind to CNTFr. There are a wide range of effects induced by P-21, such as increased BDNF levels, higher AMPA receptor protein levels, (Glur2 and or Glur3), and higher Phosphorylated GSK3B levels. Higher Ki67 levels indicate higher levels of mitosis processes. Mitosis is the splitting of one cell into two cells, a vital stage of neurogenesis. There was an approximate 150% increase in mitotic cells in the dentate gyrus compared to wild-type (non Alzheimer's) after 9-month treatment with P021. It's not with every compound that you find a compound that can improve Alzheimer's beyond healthy controls! Higher DCX levels indicate the maturation of neural precursor cells. However, there is a sex-dependent difference in DCX, and almost every P021 study uses exclusively females. Most use females because Tau Diseases are more aggressive in female mice.

There are many neural activity and plasticity markers that improve after long-term P021 treatment.