Can Optineurin Protein Aggregate to Form Toxic Amyloid-Like Fibrils or Oligomers?

Beatrice Yue, PhD
University of Illinois at Chicago (Chicago, IL)
Year Awarded:
2013
Grant Duration:
July 1, 2013 to July 31, 2015
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2013110
Award Type:
Standard
Award Region:
US Midwestern

Fibril/Oligomer Formation by Optineurin In Vitro

Summary

Protein aggregation into multimers, or the so-called amyloid fibers, is a hallmark in neurodegenerative disorders such as Alzheimer’s disease. As glaucoma is considered to be an “ocular Alzheimer’s disease,” Dr. Yue and colleagues are interested in learning whether the optineurin protein, a product of glaucoma disease gene, is similarly capable of forming aggregates and causing problems, especially in situations where optineurin is found to be mutated. If so, Dr. Yue will find a way to minimize or prevent the aggregation for developing future therapies in the clinic.

Details

Using modern biophysical and biochemical methods, Dr. Yue intends to find ways to minimize, prevent, or avert (rescue) the optineurin aggregation and toxicity.

When the study is complete, the field of glaucoma will be able to answer, for the first time, the following question: Can optineurin aggregate to form toxic amyloid fibrils or oligomers? The rescue experiments will provide important information for the development of therapies to prevent optineurin-related glaucoma.

Publications

Ying H, Turturro S, Nguyen T, Shen X, Zelkha R, Johnson EC, Morrison JC, Yue BY. Induction of autophagy in rats upon overexpression of wild-type and mutant optineurin gene. BMC Cell Biol. 2015 May 6;16(1):14. doi: 10.1186/s12860-015-0060-x. PubMed PMID: 25943884; PubMed Central PubMed Icon Google Scholar Icon