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Bryostatin 1 is a natural macrolide isolated from the bryozoan Bugula neritina and is a potent and central nervous system (CNS)-permeable PKC modulator. Bryostatin 1 binds to the isolated C1 domain of Munc13-1 and the full-length Munc13-1 protein with K_is of 8.07 nM and 0.45 nM, respectively. Bryostatin 1 has anti-cancer, anti-inflammatory, neuroprotective, anti-HIV-1 infection properties.

Bryostatin 1 (1 µM; 5 minutes; HT22 cells) treatment successfully recruits Munc13-1 from the cytosol to the plasma membrane. Effects of Bryostatin 1 on the other Munc13 family members, ubMunc13-2 and bMunc13-2, resembled those of Munc13-1 for translocation .
The increased level of expression of Munc13-1 following a 24 h incubation with Bryostatin 1 in both HT22 and primary mouse hippocampal cells is observed.
Bryostatin 1 can also affect the immune system by modulating dendritic cells (DCs) via toll-like receptor 4 (TLR4) through the MyD88-independent pathway, which favors an anti-inflammatory environment by inducing a type 2 phenotype that promotes the differentiation of CD4 T-helper (Th) lymphocytes into Th2 versus Th1 effector cells.

Bryostatin 1 (30 μg/kg; intraperitoneal injection; 3 d per week; for 2 weeks; C57BL/6J mice) treatment abolishes the onset of EAE.

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