Description
Bryostatin 1 is a macrolide lactone found in Bugula that exhibits neuroprotective, cognition enhancing, immunomodulatory, and anticancer chemotherapeutic activities. Bryostatin 1 activates PKC when administered acutely or in low doses and inhibits PKC when administered chronically or in high doses. Bryostatin 1 is currently in clinical trials as a co-administered chemotherapeutic in the treatment of various types of cancer. In animal models, this compound increases memory acquisition and storage. Additionally, bryostatin 1 activates PKD and decreases expression of β-catenin in vitro. In cellular models of Alzheimer’s disease, bryostatin 1 activates APP processing by α-secretase, decreasing levels of amyloid-β (Aβ). Bryostatin 1 improves MHC class II antigen presentation by CD4+ T cells in cellular models of Burkitt’s lymphoma and also activates toll-like receptor 4 (TLR4), inducing release of Th4 cytokines.
References
Irie K, Yanagita RC. Synthesis and biological activities of simplified analogs of the natural PKC ligands, bryostatin-1 and aplysiatoxin. Chem Rec. 2014 Apr;14(2):251-67. PMID: 24677503.
Yi P, Schrott L, Castor TP, et al. Bryostatin-1 vs. TPPB: dose-dependent APP processing and PKC-α, -δ, and -ε isoform activation in SH-SY5Y neuronal cells. J Mol Neurosci. 2012 Sep;48(1):234-44. PMID: 22700373.
Hossain A, God JM, Radwan FF, et al. HLA class II defects in Burkitt lymphoma: bryostatin-1-induced 17 kDa protein restores CD4+ T-cell recognition. Clin Dev Immunol. 2011;2011:780839. PMID: 22162713.
Ariza ME, Ramakrishnan R, Singh NP, et al. Bryostatin-1, a naturally occurring antineoplastic agent, acts as a Toll-like receptor 4 (TLR-4) ligand and induces unique cytokines and chemokines in dendritic cells. J Biol Chem. 2011 Jan 7;286(1):24-34. PMID: 21036898.
Jaggi M, Chauhan SC, Du C, et al. Bryostatin 1 modulates beta-catenin subcellular localization and transcription activity through protein kinase D1 activation. Mol Cancer Ther. 2008 Sep;7(9):2703-12. Erratum in: Mol Cancer Ther. 2009 May;8(5):1398. PMID: 18765827.
Kuzirian AM, Epstein HT, Gagliardi CJ, et al. Bryostatin enhancement of memory in Hermissenda. Biol Bull. 2006 Jun;210(3):201-14. PMID: 16801495.
