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Respiratory diseases

Hitting the MARCKS

Nature Reviews Drug Discovery volume 3, page 114 (2004)Cite this article

In a previous in vitro study, Adler and colleagues showed that an N-terminal 24-amino-acid fragment of MARCKS, known as MANS, attenuated mucin secretion in a concentration-dependent manner, presumably by competitively inhibiting the binding of MARCKS to the membranes of mucin-secreting granules within epithelial cells. Now the team has shown that intratracheal instillation of MANS blocks mucus hypersecretion in a mouse model of asthma.

Mucin secretion at rates fivefold greater than baseline was elicited in ovalbumin-sensitized mice by administration of aerosolized methacholine. Pretreatment with MANS inhibited this hypersecretory response in a concentration-dependent manner, whereas a missense N-terminal sequence of MARCKS had no effect. Basal levels of mucin secretion in non-methacholine-exposed mice were also lowered by MANS treatment.

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References

ORIGINAL RESEARCH PAPER

  1. Singer, M. et al. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nature Med. 11 January 2004 (doi:10.1038/nm983)

FURTHER READING

  1. Li, Y. et al. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. J. Biol. Chem. 276, 40982–40990 (2001)

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  2. Corry, D. B. Emerging immune targets for the therapy of allergic asthma. Nature Rev. Drug Discov. 1, 55–64 (2002)

    Article  CAS  Google Scholar 

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Authors
  1. Suzanne Farley
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Farley, S. Hitting the MARCKS. Nat Rev Drug Discov 3, 114 (2004). https://doi.org/10.1038/nrd1317

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