Therapeutic targets in focal and segmental glomerulosclerosis.

Published

Journal Article (Review)

PURPOSE OF REVIEW: Focal and segmental glomerulosclerosis occurs due to a defect in the glomerular filtration barrier. This review highlights contributions from the past year that have enhanced our understanding of the pathophysiology of focal and segmental glomerulosclerosis with emphasis on discoveries which may lead to the identification of therapeutic targets. RECENT FINDINGS: Slit diaphragm proteins have become increasingly important in signal transduction and in mediating downstream events. Actin polymerization occurs after the podocin-nephrin-Neph-1 complex is phosphorylated by Src kinase and Fyn. Recent studies of angiotensin receptor antagonists, corticosteroids and erythropoietin unravel new mechanisms that ameliorate proteinuria by targeting the cell cycle within the podocyte. The discovery that an N-acetylmannosamine kinase (MNK) mutant mouse has glomerulopathy is suggestive that human sialylation pathways may represent therapeutic targets. Proteinuria before podocyte effacement demonstrated in laminin-beta2 null mice highlights the importance of the glomerular basement membrane. Interferon-beta reduced proteinuria in three models of kidney injury, showing greatest effect on glomerular endothelial cells in vitro. SUMMARY: Basic research has illuminated mechanisms by which classic therapies have antiproteinuric effects directly on the podocyte. As knowledge expands with improved molecular techniques, understanding signaling pathways in health and proteinuric states should lead to potential therapeutic targets in focal and segmental glomerulosclerosis.

Full Text

Duke Authors

Cited Authors

  • Lavin, PJ; Gbadegesin, R; Damodaran, TV; Winn, MP

Published Date

  • July 2008

Published In

Volume / Issue

  • 17 / 4

Start / End Page

  • 386 - 392

PubMed ID

  • 18660675

Pubmed Central ID

  • 18660675

International Standard Serial Number (ISSN)

  • 1062-4821

Digital Object Identifier (DOI)

  • 10.1097/MNH.0b013e32830464f4

Language

  • eng

Conference Location

  • England