Featured publications

 

Plant extract gives hope for infant MND

Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy. Wishart TM, Mutsaers CA, Riessland M, Reimer MM, Hunter G, Hannam ML, Eaton SL, Fuller HR, Roche SL, Somers E, Morse R, Young PJ, Lamont DJ, Hammerschmidt M, Joshi A, Hohenstein P, Morris GE, Parson SH, Skehel PA, Becker T, Robinson IM, Becker CG, Wirth B, Gillingwater TH. J Clin Invest. 2014 Apr 1;124(4):1821-34. doi: 10.1172/JCI71318. Epub 2014 Mar 3.

JCI Press Pic
A study led by Euan MacDonald Centre Investigator Professor Tom Gillingwater has found that a plant pigment called quercetin – found in some fruits, vegetables, herbs and grains – could help to prevent the damage to nerves associated with the childhood form of motor neurone disease, spinal muscular atrophy.

The team has found that the build-up of a specific molecule inside cells – called beta-catenin – is responsible for some of the symptoms associated with the condition. In tests on zebrafish, flies and mice, scientists found that treating the disease with purified quercetin – which targets beta-catenin – led to a significant improvement in the health of nerve and muscle cells.

Quercetin did not prevent all of the symptoms associated with the disorder but researchers hope that it could offer a useful treatment option in the early stages of disease. They now hope to create better versions of the chemical that are more effective than naturally occurring quercetin.

These findings have come about because of a collaboration among five Euan MacDonald Centre Principal Investigators — Tom Wishart, Simon Parson, Paul Skehel, Catherina Becker and Tom Gillingwater — and is an excellent example of the benefits that membership of the Centre brings.

For press coverage of this story, see www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-26419498.

 

Fish eggs are more than just caviar

Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration. Reimer MM, Norris A, Ohnmacht J, Patani R, Zhong Z, Dias TB, Kuscha V, Scott AL, Chen YC, Rozov S, Frazer SL, Wyatt C, Higashijima S, Patton EE, Panula P, Chandran S, Becker T, Becker CG. Dev Cell. 2013 Jun 10;25(5):478-91. doi: 10.1016/j.devcel.2013.04.012. Epub 2013 May 23.

Regenerative neurology researchers are often interested in trying to understand how the nervous system develops during the development of an embryo. Perhaps the same chemical signals that drive embryonic stem cells to develop into a network of nerves and supporting cells during development could be harnessed to do the same in an adult. This would open up the possibility of regenerating a nervous system damaged by neurodegenerative disease.

Zebrafish are a very useful tool to study nervous system development and regeneration. The fundamental cell types are the same as in people, but zebrafish have an amazing capacity to regenerate nerves after damage. Importantly, the developing embryos are transparent, which makes it a lot easier to see what ‘s going on.

Professor Catherina Becker studies motor neuron development and regeneration in zebrafish. In this paper, she and her team demonstrated that nervous system regeneration in the spinal cord of the zebrafish is dependent on messages from the brain consisting of a chemical called dopamine. These are the very same messages that drive nerve development in the zebrafish embryo.

Our work sheds light on the way in which motor neurons develop and re-generate, and could inform research that leads to an increased understanding of motor neuron disease and spinal cord injuries. Professor Catherina Becker.

For press coverage of this study, see www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-22646498

ECAS: a screen to detect changes in thinking and behaviour

Screening for cognition and behaviour changes in ALS. Abrahams S, Newton J, Niven E, Foley J, Bak TH. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Jun 19. [Epub ahead of print]

brain white matter tracts_webSome people with MND experience changes in their thinking, emotion, language and behaviour together with their motor symptoms. These are collectively called cognitive symptoms. These cognitive symptoms are difficult to study because many tests rely on a rapid response and are therefore not suitable for people with a physical disability.

Here, a team led by Sharon Abrahams present the Edinburgh Cognitive ALS Screen (ECAS), developed for MND/ALS patients with physical disability for use by health care professionals. The screen is designed to detect the specific profile of cognitive and behaviour changes in patients and to differentiate it from other disorders.

Importantly, this screen provides an essential first step to managing these symptoms.

Using flies to understand nerve damage

Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis. Forrest S, Chai A, Sanhueza M, Marescotti M, Parry K, Georgiev A, Sahota V, Mendez-Castro R, Pennetta G. Hum Mol Genet. 2013 Jul 1;22(13):2689-704. doi: 10.1093/hmg/ddt118. Epub 2013 Mar 13.

fruit_fly_picThe humble fruit fly (scientific name Drosophila melanogaster) has been used in research for over 100 years. Fruit flies share 75% of their genes with humans, and many of their basic biological processes are in common. Early studies of the inheritance of visible traits have latterly become hi-tech, large-scale studies of genetics and gene manipulation. The fruit fly is easy to keep and maintain in large numbers and therefore makes an ideal “model organism”.

Giusy Pennetta and colleagues are working on a Drosophila gene called DVAP. This is the fly equivalent of a human gene called VAPB, which, when mutated, can cause MND. The researchers are trying to understand the normal function of DVAP in Drosophila cells, and, using clever genetics, the effect of deliberately mimicking the MND-associated mutation. They found that disrupting DVAP led to abnormalities in the transport of proteins along nerves and in communication between different nerves. These abnormalities eventually caused neurodegeneration (nerve death).

These similarities with human MND mean that the Pennetta lab has a useful model that they can use to unravel the details of what causes neurodegeneration and, ultimately, how to stop it.