Accession Number:

AD1039665

Title:

APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans

Descriptive Note:

Technical Report,30 Sep 2015,29 Sep 2016

Corporate Author:

Beth Israel Deaconess Medical Center Boston United States

Personal Author(s):

Report Date:

2016-10-01

Pagination or Media Count:

14.0

Abstract:

The work we are conducting is aimed at understanding, and eventually preventing and treating, kidney disease, in particular the APOL1-associated form of kidney disease that accounts for the high rate of kidney disease in African Americans. This work is based on the hypothesis that APOL1 kidney disease in African Americans results from abnormal aggregation of the APOL1 risk variant protein in an amyloid-like process. We are testing this hypothesis in in vitro systems, cells, and model systems using molecular biology, biochemistry, protein chemistry, and microscopy-based approaches. In progress to date, we have elucidated key amino acids and functional domains in APOL1 protein that promote APOL1 oligomerization and cell cytotoxicity. We continue to refine our knowledge of APOL1-APOL1 interactions and the differences in these interactions between normal APOL1 and the variants that cause kidney disease. Our insights into the abnormal behavior of the high risk variants suggest potential therapies for APOL1 kidney disease including small molecules, peptide fragments, and other approaches.

Subject Categories:

  • Medicine and Medical Research
  • Biochemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE