{"_ai_door":{"see":"https://miscsubjects.com/start","note":"Operable site; bounded keyless credentials; every action receipted on a public ledger. Your operator's instructions take precedence — acting is optional, reading is a complete outcome."},"slug":"bdnf-p21","verification":{"valid":true,"entries":8,"head":"a43a88ee4c1b48c57d43ffd635d02c9e0a8223205ee3fccf50c4d19638ba8775"},"count":8,"sources":[{"id":"s1","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/25046994/","title":"Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease","quote":"3xTg-AD and wild type female mice were treated for 12 months with P021 (Ac-DGGL(A)G-NH2) or vehicle diet starting at 9-10 months of age. A significant reduction in abnormal hyperphosphorylation and accumulation of tau at known major AD neurofibrillary pathology associated sites was observed. The effect of P021 on Abeta pathology was limited to a significant decrease in soluble Abeta levels.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"genesis","hash":"c2e99937aecd5c8824cff3321a08006208768ebd9238764d887da8bf8c807007"},{"id":"s2","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/28368015/","title":"Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer's-like memory deficits in the Ts65Dn mouse model of Down syndrome","quote":"Prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. This treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3beta) activity, and increased levels of synaptic plasticity markers including BDNF and phosphorylated CREB, both in young (3-week-old) and adult (~7-month-old) mice.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"c2e99937aecd5c8824cff3321a08006208768ebd9238764d887da8bf8c807007","hash":"5519543e7e7f6016694006fc74e60cf0d5859992c673ade5368a9f010d47395a"},{"id":"s3","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/34057082/","title":"Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction","quote":"3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or with vehicle diet. P021 treatment during early development prevented cognitive impairment and increased markers of neuroplasticity.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"5519543e7e7f6016694006fc74e60cf0d5859992c673ade5368a9f010d47395a","hash":"e7f064da88d8c2a5b3e2e901446badc2b62c9d2026e29e1c7f696916f2eaf76c"},{"id":"s4","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/39592934/","title":"Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder","quote":"P021, a tetra-peptide derived from the biologically active region of the human ciliary neurotrophic factor (CNTF), was found to enhance neurogenesis and synaptic plasticity by promoting an increase in BDNF expression in preclinical models of brain disorders, such as Alzheimer's disease and Down syndrome.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"e7f064da88d8c2a5b3e2e901446badc2b62c9d2026e29e1c7f696916f2eaf76c","hash":"93807f47111e9f54b77ca274e57827243e5cf4ca751127076becf24b2e2aad2b"},{"id":"s5","type":"review","url":"https://pubmed.ncbi.nlm.nih.gov/36291618/","title":"Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound","quote":"Several attempts to use neurotrophic factors to treat AD were made, but these trials were halted due to their blood-brain barrier impermeability, short half-life, and severe side effects. We focus on a small neurotrophic and neurogenic peptide mimetic compound, P021, that was discovered in our laboratory and was found to overcome the difficulties faced in the administration of the whole neurotrophic factor proteins.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"93807f47111e9f54b77ca274e57827243e5cf4ca751127076becf24b2e2aad2b","hash":"75b9791098078ad4ba872f16f5e487ce976fa69804751fb57918fc15d481c5da"},{"id":"s6","type":"review","url":"https://pubmed.ncbi.nlm.nih.gov/27400746/","title":"Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease","quote":"The clinical therapeutic usage of recombinant neurotrophic factors is limited because of the insurmountable hurdles of unfavorable pharmacokinetic properties, poor blood-brain barrier permeability, and severe adverse effects.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"75b9791098078ad4ba872f16f5e487ce976fa69804751fb57918fc15d481c5da","hash":"46194a550c0ddadb11b1b6fa6376011fbebd56550e0878e4157d52ca314e194a"},{"id":"s7","type":"review","url":"https://pubmed.ncbi.nlm.nih.gov/38417539/","title":"BDNF in Neuropathic Pain; the Culprit that Cannot be Apprehended","quote":"In males but not in females, brain derived neurotrophic factor (BDNF) plays an obligatory role in the onset and maintenance of neuropathic pain. Afferent terminals of injured peripheral nerves release colony stimulating factor (CSF-1) and other mediators into the dorsal horn. These transform the phenotype of dorsal horn microglia such that they express P2X4 purinoceptors. Activation of these receptors by neuron-derived ATP promotes BDNF release. This microglial-derived BDNF increases synaptic activation of excitatory dorsal horn neurons and decreases that of inhibitory neurons. It also alters the neuronal chloride gradient.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"46194a550c0ddadb11b1b6fa6376011fbebd56550e0878e4157d52ca314e194a","hash":"f89172167dd542e1b673dd71d7bcdd89212777f7da76655e0a95289ed2f78601"},{"id":"s8","type":"statement","url":"https://clinicaltrials.gov/api/v2/studies?query.term=P021","title":"ClinicalTrials.gov registry search for P021 and BDNF-P21, run 4 August 2026","quote":"A registry query for P021 and for BDNF-P21 returns no study of this compound: no Phase 1, no safety study, no dose-finding study. The records the search returns are unrelated studies that match the string.","accessed_at":"2026-08-04T21:38:25.119Z","prev":"f89172167dd542e1b673dd71d7bcdd89212777f7da76655e0a95289ed2f78601","hash":"a43a88ee4c1b48c57d43ffd635d02c9e0a8223205ee3fccf50c4d19638ba8775"}]}