Spasticity gene finding provides clues to causes of nerve cell degeneration

January 9, 2012

The discovery of a gene that causes a form of hereditary spastic paraplegia (HSP) may provide scientists with an important insight into what causes axons, the stems of our nerve cells, to degenerate in conditions such as multiple sclerosis.

In the today, an international team of scientists led by Dr Evan Reid at the University of Cambridge, and Dr Stephan Zuchner from the University of Miami, report that mutations in the gene known as 'reticulon 2' on chromosome 19 cause a form of HSP, a condition characterised by progressive and (spasticity) of the legs, caused by selective and specific degeneration of axons

The team identified three mutations in the reticulon 2 gene as causing a type of HSP – in one case, this mutation included an entire deletion of the gene. In addition, the researchers showed that reticulon 2 interacts with another gene, spastin. in this latter gene cause the most common form of hereditary spastic paraplegia.

Reticulon 2 provides the genetic code for a reticulon protein that is a member of a family of proteins recently shown to play a key role in shaping the endoplasmic reticulum. The endoplasmic reticulum is a network of interconnected sheets and tubules that extends throughout the cytoplasm in nearly all cells. It has a number of functions, including protein synthesis, calcium signalling and regulation of other components of the cell. Recent data suggest that the sheets are involved in protein synthesis, whereas the tubules are specialised to carry out the other functions.

This new study provides the most direct evidence to date that defects in how the endoplasmic reticulum is shaped and formed could underlie axon degeneration. When axons degenerate, signals are unable to pass through the , leading to a breakdown of communication within the central nervous system. This is common in degenerative diseases of the nervous system, such as multiple sclerosis.

"Our work highlights important new disease mechanisms, which may provide a platform for us to study how axons are damaged in devastating illnesses such as HSP, and perhaps even in , which in some cases is very similar to HSP," explains Dr Reid, a Wellcome Trust Senior Research Fellow in Clinical Science. "But we must not forget how this work may immediately directly benefit families affected by hereditary spastic paraplegia, for whom the discovery now opens up the possibility of genetic counselling and testing."

Explore further: Study offers new clues about hereditary spastic paraplegia

More information: Mutations in the ER-shaping protein cause the axon-degenerative disorder hereditary spastic paraplegia type 12, Journal of Clinical Investigation.

Related Stories

Study offers new clues about hereditary spastic paraplegia

July 8, 2011

(Medical Xpress) -- New research from Rice University and Italy's Eugenio Medea Scientific Institute is yielding clues about hereditary spastic paraplegia (HSP), a group of inherited neurological disorders that affect about ...

Recommended for you

Questions, concerns about 'three-parent' baby

September 28, 2016

The surprise announcement that a healthy baby boy was born from a new technique mixing the DNA of two women and a man raises as many questions—scientific and ethical—as it settles, experts said Wednesday.

How our cells use mother's and father's genes

September 28, 2016

Researchers at Karolinska Institutet and Ludwig Institute for Cancer Research have characterized how and to what degree our cells utilize the gene copies inherited from our mother and father differently. At a basic level ...

Regulatory RNA essential to DNA damage response

September 26, 2016

Stanford researchers have found that a tumor suppressor known as p53 is stabilized by a regulatory RNA molecule called DINO. The interaction helps a cell respond to DNA damage and may play a role in cancer development and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.