October 25, 2018

Arzanol - A NEW Brain Glycogen Phosphorylase (bGP) Agonist

Arzanol is a prenylated heterodimeric phloroglucinyl α-pyrone, isolated from Helichrysum italicum L., a plant of perfumery relevance and used in herbal medicine. This anti-inflammatory compound has a broad polypharmacological profile, shows antioxidant activity in vitro and in vivo, inhibits NF-κB activation as well as HIV-1 replication in T cells, and inhibits critical enzymes of the inflammatory cascade (PGES-1, 5-LOX and COX-1), consequently modulating the release of pro-inflammatory mediators (interleukins, TNFα, and PGE2).

In a recent study, F. del Gaudio, et al. showed by using MS-based chemical proteomics, that arzanol is a high affinity agonist of brain glycogen phosphorylase (bGP). Arzanol directly interacts with bGP, competing for the same allosteric binding site on bGP like AMP (but with higher affinity), inducing similar conformational changes and promoting the transition to the active form, consequently leading to increased bGP enzyme activity. GPs are key enzymes in glycogen metabolism, promoting the rate-limiting step of its mobilization. In brain, glycogen acts as an emergency glucose storage to protect neurons against hypoglycemia and hypoxic stress, being critical for high cognitive processes such as learning and memory consolidation. Since reduced glycogen breakdown is associated with impaired cognitive functions and neuro-degeneration, the activation of glycogen breakdown might be a new therapeutic strategy.

LIT: Chemoproteomic fishing identifies arzanol as a positive modulator of brain glycogen phosphorylase: F. del Gaudio, et al.; Chem. Commun. (ePub ahead of print) (2018)

February 24, 2018

BAFF and APRIL Inhibitors to study Mice Autoimmunity

The TNF superfamily ligands, BAFF and APRIL, are involved in the pathogenesis of a number of autoimmune diseases by regulating plasma cell survival. AdipoGen Life Sciences provides unique antibodies to study autoimmune diseases in mice by blockade of mouse BAFF or APRIL, such as anti-BAFF (mouse), mAb (blocking) (Sandy-2) or anti-APRIL (mouse), mAb (rec.) (blocking) (Apry-1-1).

In a recent study, Haselmayer et al., tested several inhibitors of BAFF or APRIL in a model of mouse autoimmune disease (SLE) to confirm that inhibition of mouse BAFF and APRIL by the receptor TACI-Fc is more efficient than inhibition of BAFF alone or APRIL alone on long-lived plasma cell survival. To block mouse APRIL in this study, anti-APRIL (mouse), mAb (rec.) (blocking) (Apry-1-1) (AG-27B-0001PF) from Adipogen was injected in C57BL/6 mice.

LIT: A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells: P. Haselmayer, et al.; Eur. J. Immunol. 47, 1075 (2017)

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