- Commonly prescribed drugs affect decisions to harm oneself and others
- Research reveals how the human brain might reconstruct past events
- Research into genetic influences on epilepsy and migraines
- Fast forwarding treatment for neurodegenerative disorders at LWENC
- Natural genetic variation gives complete resistance in prion diseases
- Professor Lees awarded ABN Medal 2015
- Professor Hardy elected member of EMBO
- Working with Saracens to monitor concussion in rugby
- Mutations in two novel genes cause primary dystonia
- A new genetic switch uncovered in the long genes expressed in our brain
- Professor Alan Thompson elected to the Fellowship of the Academy of Medical Sciences
- UCL Institute of Neurology researchers awarded MRC fellowships
- Professor Ray Dolan has been elected Member of the European Academy of Sciences and Arts
- Deep brain stimulation for Tourette syndrome
- Behaviour changes common in early stage familial Alzheimer's
- Imaging shows early brain changes in FTD patients
- New test measures deadly protein in Huntington’s disease patients’ spinal fluid
- Professor Mary Reilly is elected to be the first female President of the Association of British Neurologists in 83 years
- Structure of genetic messenger molecules reveals key role in diseases
- Professor Nick Fox speaks about trial in early onset familial Alzheimer's disease at UCL
- First major exhibition to explore BSE and its impact opens at Hayward Gallery
- Government pledges £300m for dementia research
- UCL awarded £10m to develop new dementia treatments
- BRC awards £700,000 to neuroscience projects
- UCL Neuroscience rated top by research strength in the REF2014
- $5.9 million boost for SUDEP research
- Secret of tetanus toxicity offers new way to treat motor neuron disease
- Harm to others outweighs harm to self in moral decision making
- Auto anomaly detection for brain imaging awarded £1m grant
- Spinal surgery: OECs studies to start in 2015
- New brain tumour research Centre of Excellence is unveiled
- UCL awarded £13.5 million to advance medical research facilities
- UCL research helps paralysed man to recover function
- Stenting safe and effective for long-term stroke prevention
- Department of Clinical & Experimental Epilepsy re-designated as a WHO Collaborating Centre
- Leonard Wolfson Experimental Neurology Centre open evening
- Brain stimulation to improve cognition in dementia
- Professor Lees receives Jay Van Andel Award for Outstanding Research in Parkinson’s Disease
- Creating brain cells from skin to study Alzheimer's
- Queen Square authors prominent in Brain collection of classic articles
- Toxic proteins implicated in frontotemporal dementia and motor neurone disease
- GCH1 gene and Parkinson’s risk
- Double mutation linked to frontotemporal dementia
- Equation to predict happiness
- Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia
- Researchers test whether diabetes drug can help Parkinson’s patients
- Acute optic neuritis: a review and proposed protocol
- Hippocampal subfield size predicts the precision of memory recall
- Immune system implicated in dementia development
- UCL and Chiesi Group announce partnership to develop a novel therapeutic for birth asphyxia
- Professor Golay made a Fellow of the ISMRM
- The new Leonard Wolfson Experimental Neurology Centre (LWENC) has opened for clinical studies and trials
- Professor Rees wins UCLU Student Choice Teaching Award
- New epilepsy treatment offers ‘on demand’ seizure suppression
- Professor Tabrizi and Professor Price elected to Fellowship of the Academy of Medical Sciences.
- Professor Dolan and Professor Friston elected to EMBO membership
- Vitamin B3 treatment for ataxia shows promise in first human trial
- Teaching Awards 2014
- Light-activated neurons from stem cells restore function to paralysed muscles
- UCL and Max Planck Society invest €5m to open world’s first computational psychiatry centre
- Successful launch of new annual leading edge neurology course
- Statins could help control MS
- Professor Hardy awarded Thudichum Medal by Biochemical Society
- Population Screening for vCJD Using a Novel Blood Test
- Chief Medical Officer appoints Professor Rossor as NIHR National Director for Dementia Research
- New partnership between UCLP brain tumour scientists and Brain Tumour Research
- Professor Hardy awarded Dan David Prize for work on the amyloid gene encoding APP
- NIHR award £650,000 for research into rare neurodegenerative and neuromuscular diseases
- Lowering levels of toxic protein reverses abnormalities in cells from patients with Huntington's disease
- Teaching Awards 2015
Toxic proteins implicated in frontotemporal dementia and motor neurone disease
11 August 2014
Scientists at UCL Institute of Neurology and the Max Planck Institute for Biology of Ageing in Cologne have discovered how a specific genetic mutation may damage nerve cells in frontotemporal dementia and motor neurone disease.
The research, which suggests a potential new target for
treating the two brain diseases, was funded by Alzheimer’s Research UK, the
Motor Neurone Disease Association, the UK Medical Research Council (MRC) and the
Wellcome Trust. The study was published in the journal Science.
The researchers used fruit flies to better understand the
effects of the C9orf72 gene, which has been linked to both frontotemporal
dementia (FTD) and motor neurone disease.
A faulty version of the C9orf72 gene was recently shown to cause both FTD and motor neurone disease, and is thought to be responsible for roughly 8% of all cases of each disease in the UK.
The faulty gene contains a short section of genetic code
that is repeated thousands of times. This repeated code results in extra
molecules called RNA, as well as repeated fragments of protein, and the
challenge has been to uncover whether the RNA or the protein – or both – may be
harmful to nerve cells.
These results suggest a key role for these toxic proteins in FTD and motor neurone disease, and the next step will be to understand whether drugs could be designed to target these proteins and stop the death of nerve cells. We believe these results mark an important advance in our understanding of these neurodegenerative diseases, and we are excited to follow up these findings.
Dr Adrian Isaacs, senior author, Department of Neurodegnerative Disease, UCL Institute of Neurology
The research team first worked to ‘clone’ sections of DNA in
a way that produced only RNA, only protein fragments, or RNA and protein
together. They then used fruit flies to study the effects of both the RNA and protein.
They found that although RNA on its own did not result in any damage to nerve
cells, artificial DNA that produced RNA and protein, or only protein, caused
striking damage to nerve cells and shortened the lifespan of the flies.
The results suggest that toxic protein fragments are the main culprit in causing brain cell death in both diseases.
Further experiments showed that the toxic effects could be traced to two particular types of protein fragment – those containing high amounts of an amino acid called arginine.
Dr Adrian Isaacs of UCL’s Institute of Neurology, senior author of the research, said:
“Our findings were also surprising because our earlier results showed that people with FTD have a build-up of RNA in certain brain regions, and one future avenue for research will be to determine what role this RNA build-up may play in the disease.”
- S Mizielinska et al. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science. Available online 7 August 2014. DOI: 10.1126/science.1256800
- UCL press release
- Alzheimer's Research UK press release
- Lashley T, et al. A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia. Neuropathol Appl Neurobiol. 2014 Jun;40(4):502-13. doi: 10.1111/nan.12100.
- Mizielinska S, et al. C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci. Acta Neuropathol. 2013 Dec;126(6):845-57. doi: 10.1007/s00401-013-1200-z.
- Dr Adrian Isaacs' academic profile on IRIS
Image: The brain of a transgenic fruit fly Drosophila melanogaster, used to study neurodegenerative diseases, with cell nuclei (stained purple) and glial cells (green). (Courtesy of Teresa Niccoli, UCL Institute of Healthy Ageing)
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