A study has offered new insights into the mechanisms behind progeria, an incurable disease that causes premature ageing.
Dr Roland Foisner at the Max F. Perutz Laboratories of the University of Vienna and the Medical University of Vienna, Austria, hope their findings will open new avenues for specific treatments for the disease.
Writing in Genes & Development, Dr Foisner and his team are examining why and how progerin impairs the production of ECM proteins.
The protein progerin, a mutant version of lamin A protein, is known to be responsible for many of the characteristics of the disease but the team is investigating the molecular functions of nuclear lamins and their mutated forms such as progerin and associated diseases.
“A few years ago, we and others found that progeria cells have much less LAP2a than normal cells. LAP2a is a protein that interacts with lamin A to regulate cell proliferation, the process that produces new cells. Interestingly, LAP2a levels also decrease during normal aging,” said Dr Foisner, deputy director of the Department of Medical Biochemistry of the Medical University of Vienna.
The researchers found that when LAP2a was re-introduced, they could rescue the proliferation defect of the progeria cell line.
Further experiments revealed that LAP2a functions very differently in progeria cells compared to normal cells.
Rather than binding to a distinct nuclear pool of lamin A and slowing proliferation, in progeria the cells proliferate much slower and prematurely enter the cellular ageing process because they do not have the nuclear lamin A pool.
This means that LAP2a uses a different route to exercise its function in progeria cells.
“Cells are surrounded by material that structurally supports them. It is called extracellular matrix or in short ECM,” said researcher Sandra Vidak.
“It was reported before that progerin negatively affects the production of ECM proteins, leading to a disrupted cellular environment and slower proliferation.
“Now we connected this to the low LAP2a levels and when we reintroduced LAP2a into progeria cells they again produced normal ECM and proliferated normally and didn’t enter the cellular aging process.”
Vidak S, Kubben N, Dechat T, Foisner R. Proliferation of progeria cells is enhanced by Lamina-associated polypeptide (LAP) 2a through expression of extracellular matrix proteins. Genes & Development September 2015; doi:10.1101/gad.263939.115.
Photo of Zoey, aged four, from USA, courtesy of Progeria Research Foundation
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