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Charting a TRP to Novel Therapeutic Destinations for Kidney Diseases

Juan Lorenzo Pablo1, Anna Greka1

  • 1Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Trends in Pharmacological Sciences
|November 10, 2019
PubMed

Insights

Targeting TRP channels offers new hope for kidney disease. Blocking TRPC5 protects kidney filters, showing potential for treating focal segmental glomerulosclerosis (FSGS) and other kidney disorders.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genetics

Background:

  • Ion channel dysfunction is implicated in various kidney diseases.
  • The transient receptor potential (TRP) channel superfamily plays crucial roles in kidney homeostasis and pathogenesis.
  • Dysregulation of TRP channels contributes to kidney damage and disease progression.

Purpose of the Study:

  • To highlight the therapeutic potential of targeting TRP channels for kidney diseases.
  • To identify specific TRP channels as viable drug targets for kidney disorders.
  • To explore the role of TRPC5 in focal segmental glomerulosclerosis (FSGS).

Main Methods:

  • In vitro and in vivo studies investigating TRPC5 channel blockers.
  • Analysis of human genetics data linking TRP channels to kidney diseases.
  • Review of existing literature on TRP channel function in the kidney.

Main Results:

  • TRPC5 blockers demonstrated protective effects on kidney filter components in experimental models.
  • TRPC5 was identified as a potential therapeutic target for FSGS.
  • TRPC6, PKD2, and TRPM6 were identified as plausible targets for FSGS, polycystic kidney disease, and familial hypomagnesemia with secondary hypocalcemia, respectively.

Conclusions:

  • Targeting TRP channels presents a promising therapeutic strategy for kidney diseases.
  • TRPC5 represents a tractable target for developing treatments for FSGS.
  • Further research into TRP channel modulation could lead to novel therapies for a range of kidney disorders.
Keywords:
AC1903FSGSTRPC5TRPC6ion channelspodocyte

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