Table of Contents

Viewpoints

• • Elizabeth R. Sharlow,
  • Max Grögl,
  • Jacob Johnson,
  • and John S. Lazo

  Anti-leishmanial Drug Discovery: Rising to the Challenges of a Highly Neglected Disease

  Mol Interv April 2010 10:72-75; doi:10.1124/mi.10.2.4
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  In much of the developing world, leishmaniasis is endemic, infecting millions of people each year, with almost a half-billion people at risk of infection. There are three major clinical manifestations of leishmaniasis, each having significant cultural and socioeconomic impact, owing to disability, disfigurement, and death. Despite its prevalence and profound consequences for human life, leishmaniasis remains a neglected disease with very limited therapeutic options. Recently, some large-scale anti-leishmanial drug-discovery campaigns have been initiated; however, these efforts have focused primarily on one leishmanial manifestation, the visceral form, leaving the cutaneous forms of leishmaniasis even further neglected. We discuss the impact of leishmaniasis and its primary clinical manifestations, the transmission and the life cycle of the Leishmania parasite, available treatments, and the new efforts and challenges facing drug discovery.

• • Matthew R. Young,
  • Arti N. Santhanam,
  • Noriko Yoshikawa,
  • and Nancy H. Colburn

  Have Tumor Suppressor PDCD4 and its Counteragent Oncogenic miR-21 Gone Rogue?

  Mol Interv April 2010 10:76-79; doi:10.1124/mi.10.2.5
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  A recent article suggests that the well known tumor suppressor PDCD4 also functions as a pro-inflammatory agent. The PDCD4 counteragent miR-21, a pro-oncogenic micro-RNA, is described as an anti-inflammatory agent. The authors of this research article provide evidence that mice lacking PDCD4 are protected from the lethal effects of lipopolysaccharide (LPS). This report also confirms miR-21 as a negative regulator of PDCD4 expression after LPS stimulation. Downstream mediators of the pro-inflammatory activity of PDCD4 include IL-10, an anti-inflammatory cytokine that is negatively regulated by PDCD4, and IL-6, a pro-inflammatory cytokine that appears to be upregulated in a PDCD4 dependent manner, possibly through an increase in NF-κB activity. Is it possible that a tumor-suppressor protein and an oncogenic micro-RNA can be oppositely targeted to control inflammatory disease?

• • Michael Chvanov,
  • Ole H. Petersen,
  • and Alexei V. Tepikin

  Pharmacologically Directed Cell Disposal: Labeling Damaged Cells for Phagocytosis as a Strategy against Acute Pancreatitis

  Mol Interv April 2010 10:80-85; doi:10.1124/mi.10.2.9
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  Acute pancreatitis is a common clinical condition, which lacks effective pharmacological treatment. The severity of the disease is determined by the extent of necrotic death of pancreatic acinar cells. This article discusses the idea of developing new pharmacological tools against acute pancreatitis by labeling necrotic pancreatic acinar with apoptotic “eat-me” signaling molecules. This approach could facilitate removal of dead material without activation of inflammatory response and thus would eliminate the main source of damage to the body during acute pancreatitis.