ArticleCell death and differentiation2015
PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Synthetic Preimplantation Factor (sPIF)* Improves Survival and GI Function in Acute Lethal Radiation Syndrome in a Clinically Relevant Murine Model.International journal of molecular sciences · 2026Article
- The shifting landscape of the preterm brain.Neuron · 2025Review
- miR-NPs-RVG promote spinal cord injury repair: implications from spinal cord-derived microvascular endothelial cells.Journal of nanobiotechnology · 2024Article
- Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.Cellular and molecular life sciences : CMLS · 2024Article
- Modulation of the Cellular microRNA Landscape: Contribution to the Protective Effects of High-Density Lipoproteins (HDL).Biology · 2023Review
- Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice.Scientific reports · 2022Article
- Effects of biological sex and pregnancy in experimental autoimmune encephalomyelitis: It's complicated.Frontiers in immunology · 2022Review
- Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2.JCI insight · 2021Article
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- Preimplantation Factor (PIF): a peptide with various functions.JBRA assisted reproduction · 2020Review
- Synthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth.PloS one · 2020Article
- Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice.Scientific reports · 2019Article
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- sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/let-7 and miR-21 pathways.Cell death & disease · 2019Article
- The core sequence of PIF competes for insulin/amyloid β in insulin degrading enzyme: potential treatment for Alzheimer's disease.Oncotarget · 2018Article
- Extracellular Vesicles Derived from Wharton's Jelly Mesenchymal Stem Cells Prevent and Resolve Programmed Cell Death Mediated by Perinatal Hypoxia-Ischemia in Neuronal Cells.Cell transplantation · 2018Article
- Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon.Journal of assisted reproduction and genetics · 2018Article
- PreImplantation factor (PIF) protects cultured embryos against oxidative stress: relevance for recurrent pregnancy loss (RPL) therapy.Oncotarget · 2017Article
- PIF* promotes brain re-myelination locally while regulating systemic inflammation- clinically relevant multiple sclerosis M.smegmatis model.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A synthetic peptide (sPIF) analogous to the mammalian embryo-derived PreImplantation Factor (PIF) enables neuroprotection in rodent models of experimental autoimmune encephalomyelitis and perinatal brain injury. The protective effects have been attributed, in part, to sPIF's ability to inhibit the biogenesis of microRNA let-7, which is released from injured cells during central nervous system (CNS) damage and induces neuronal death. Here, we uncover another novel mechanism of sPIF-mediated neuroprotection. Using a clinically relevant rat newborn brain injury model, we demonstrate that sPIF, when subcutaneously administrated, is able to reduce cell death, reverse neuronal loss and restore proper cortical architecture. We show, both in vivo and in vitro, that sPIF activates cyclic AMP dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) signaling, leading to increased phosphorylation of major neuroprotective substrates GAP-43, BAD and CREB. Phosphorylated CREB in turn facilitates expression of Gap43, Bdnf and Bcl2 known to have important roles in regulating neuronal growth, survival and remodeling. As is the case in sPIF-mediated let-7 repression, we provide evidence that sPIF-mediated PKA/PKC activation is dependent on TLR4 expression. Thus, we propose that sPIF imparts neuroprotection via multiple mechanisms at multiple levels downstream of TLR4. Given the recent FDA fast-track approval of sPIF for clinical trials, its potential clinical application for treating other CNS diseases can be envisioned.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.