A protein's role in progressive renal disease

Focal segmental glomerulosclerosis (FSGS) made a brief media splash last year when a kidney transplant forced NBA superstar Alonso Mourning into early retirement. Mourning's condition elicited a flood of calls from fans offering their kidneys, but most people with kidney disease are not so lucky.

Some 56,000 patients await transplants; many have waited over five years. FSGS, which underlies about 25% of the 60,000 kidney-related deaths each year, causes progressive kidney failure.

FSGS commonly occurs as an outgrowth of various primary disorders, including obesity, HIV infection, diabetes, and hypertension. Though it's not clear what causes FSGS, this form of renal pathology is becoming more common.

By using the genes underlying inherited forms of FSGS as probes, scientists hope to uncover the mechanisms that unleash the disease and to find ways to stem the damage.

Mutations in the ACTN4 gene, which encodes a protein called a-actinin-4, cause an inherited form of FSGS. The protein normally remodels actin filaments, the primary structural component of muscle and cytoskeleton.

Having a single mutated copy of the gene can cause FSGS in humans, though it is unclear how. In this issue of PLoS Biology, Martin Pollak and his colleagues at Brigham and Women's Hospital at Harvard Medical School use a three-pronged approach to figure out how the defective protein wreaks renal havoc and how these physiological changes lead to FSGS.

Using biochemical analysis, cell-based studies, and a newly developed "knockin" mouse model, the researchers report two possible mechanisms of initiating disease.

Aggregation of a-actinin-4 and the toxic affects of aggregation could injure kidney cells, or loss of a-actinin-4 function caused by rapid degradation of the protein could produce injury.

Pollak and colleagues argue that both factors likely play a role.


Contact: Susanne DeRisi
Public Library of Science

Page: 1

Related biology news :

1. Optimizing proteins death domain halts leukemia in laboratory study
2. Findings suggest need for new view of p53 cancer proteins interaction with DNA
3. Rb proteins role in retina development is key to understanding devastating eye cancer
4. Researchers view proteins structural changes in real time
5. Misfolding the key to proteins ability to kill brain cells
6. Researchers solve killer proteins crime
7. Biologists discover proteins impace on plant-water balance
8. Penn researchers proteins link to leukemia
9. Gene mutation causes progressive changes to cell structure in children with Progeria
10. Researchers develop blood test that can detect genetic changes in progressive breast cancer
11. Lions share of the best of Asias progressive minds in science and medicine convene

Post Your Comments:

(Date:11/11/2019)... ... November 11, 2019 , ... MicroGenDX, ... played a key role in the award-winning study “Next Generation Sequencing for the ... The molecular diagnostic laboratory processed samples using Next Generation DNA Sequencing to examine ...
(Date:11/9/2019)... ... , ... SiteSeer Technologies, creator of SiteSeer Professional retail site selection software, is ... SiteSeer. The boutique real estate developer of single and multi-tenant buildings on sites ranging ... own analysis of markets. , Geoffrey Kerth, manager of GPK Acquisitions, says that ...
(Date:11/9/2019)... ... November 08, 2019 , ... ... specialized histology, pathology, biomarker development, and archiving services for the biopharmaceutical, medical ... of Histo-Scientific Research Laboratories (HSRL), Vet Path Services (VPS) and Tox Path ...
Breaking Biology News(10 mins):
(Date:11/5/2019)... ... November 05, 2019 , ... Focal Healthcare , an ... its Fusion Bx 2.0 prostate fusion biopsy solution. By combining information from multiparametric ... will give urologists across Europe the ability to perform targeted transrectal and transperineal ...
(Date:11/2/2019)... ... 2019 , ... A clinical trial usually involves many different ... principal investigators, supply chain managers, manufacturers, IRT, CRAs and so on. Lack of ... data, potentially leading to patient risk. , By having a single source of ...
(Date:11/2/2019)... ... 31, 2019 , ... drug360 graph, a breakthrough knowledge graph ... brings tellic’s expertise in biomedical language processing and machine learning to bear on ... genes, diseases, variants, phenotypes, and other biomedical entities. Researchers and analysts can ...
(Date:10/30/2019)... ... 30, 2019 , ... Western University of Health Sciences held ... play in educating the next generation of health care providers. , The event, ... WesternU administrators and representatives of companies working with the University on a range ...
Breaking Biology Technology:
Cached News: