跳到主要內容區塊
Google  

 

 

:::

[2020/11/13] Research Results of NYMU have been Selected as the Cover Story of EMBO Reports: Hutchinson-Gilford Progeria Syndrome is Related to Abnormalities of the Cilia

NYMU Institute of Biochemistry and Molecular Biology Chair Professor Chen (front row middle) and his team members

 

National Yang-Ming University Institute of Biochemistry and Molecular Biology Chair Professor Chen’s research team has cooperated with Researcher Chi of the National Health Research Institutes' Institute of Biotechnology and Pharmaceutical Research to discover that an abnormality of the primary cilia is likely to be an important pathological mechanism behind Hutchinson-Gilford Progeria syndrome. This discovery not only provides a new perspective for the treatment of Progeria, but, in addition, the findings have been published in the prestigious journal EMBO Reports as its October 5thcover story.

 

Patients with Hutchinson-Gilford Progeria syndrome suffer from a failure to thrive, a loss of fat, wrinkled skin, alopecia, osteoporosis, various cardiovascular diseases and a range of joint problems. Their average age is 13. This disease was first discovered in 1886 and in 2003, the relationship of the disease with gene mutations in the LMNA was established; however the pathological mechanism remained unclear.

 

The LMNA gene expresses the protein lamin A, which is a component of the nuclear lamina that forms part of the cytoskeleton. When a LMNA gene mutation is present, the nucleus develops abnormal wrinkles and even serious deformities. In addition to being related to Progeria, gene mutations in LMNA have been linked to ten other human genetic diseases. These include Emery-Dreifuss (muscular dystrophy), and dilated cardiomyopathy; as a group these diseases are collectively called laminopathy.

 

The research results of Professor Chen’s research team were selected as the cover story of EMBO Reports

 

Professor Chen's research team first discovered that, in patients with Progeria, the skin fibroblasts have shorter and fewer primary cilia. Primary cilia function as a cell's antennas and are able to detect changes in the environment, which then causes signal transduction that induce accommodation. Hence, it was suspected that primary abnormalities of the cilia may be the pathological mechanism behind Progeria.

 

The research team created LMNA gene-deficient mice and confirmed that mice with a nuclear lamin protein insufficiency did develop abnormalities of the primary cilia in a range of organs. Using RNA interference technology, the team also found that a reduction in lamin protein expression in human retinal pigment epithelial cells also resulted in abnormalities of the primary cilia. Turning to the mechanism, the team discovered that LMNA gene deficiency causes an excessive assembly of the actin cytoskeleton and that this interferes with the formation of primary cilia. Conversely, when cytoskeleton assembly is inhibited, it can be allowed to recover and the formation of primary cilia begins again. This discovery not only helps us to understand the pathological mechanism behind Progeria and laminopathy, but also provides a new perspective for the development of treatment plans in the future. .

 

Left: most normal cells have primary cilia that functions like the antenna allowing the cell to detect environmental changes outside the cell. Right: Professor Chen’s team found out that cells with an abnormal form of the lamin protein, such as when a patient has Progeria, undergo excessive assembly of actin cytoskeleton (marked in red lines), and that this interferes with formation of primary cilia.

 

 

 

 

 

 

 

 

 

 

 


 

views