The University of Nottingham in the UK issued a press release last week about the creation of a mouse model for Lewy Body Dementia. Most medical research starts out in petri dishes and test tubes, moves to a non-primate (such as mice), and eventually -- many, many years later -- can move on to humans. So having a mouse model of LBD is significant because it now allows for medications, etc. to be tested in mice. Copied below is the text of the University's press release on the research and the impossible-to-read journal article abstract. I read this news on the Michael J Fox Foundation website today.
http://www.nottingham.ac.uk/public-affa ... -releases/
--> then use the menu on the level to get to the August 2008 press releases
Nottingham researchers in dementia breakthrough
PA189/08 â Press Release of the University of Nottingham
August 07 2008
Scientists at The University of Nottingham have made a crucial breakthrough in the battle to slow or prevent the onset of a very common type of dementia and Parkinson's disease.
The researchers have genetically produced the first ever mouse model with the type of brain degeneration, or nerve cell loss, seen in Lewy body disease and Parkinson's disease which could eventually lead to more targeted drugs to treat the degenerative conditions.
The research, published in the Journal of Neuroscience, was jointly funded by the Alzheimer's Research Trust and the Parkinson's Disease Society.
The study has been carried out by Professor John Mayer and Dr Lynn Bedford in the University's School of Biomedical Sciences in collaboration with Professor Jim Lowe in the School of Molecular Medical Sciences.
Professor John Mayer said: âCurrent drugs given to people with Lewy body and Parkinson's disease simply treat the symptoms. This model is the first platform to understand how the brain cell deterioration takes place. We will use this model to identify targets for new drugs to slow or prevent the disease.â
Lewy body disease, also known as dementia with Lewy bodies (DLB) shares characteristics with both Alzheimer's and Parkinson's diseases. Of the 700,000 people in the UK with dementia, around 15 per cent have Lewy body disease. The number of people with dementia is forecast to double within a generation.
Rebecca Wood, Chief Executive of the Alzheimer's Research Trust, said: âThis is a crucial breakthrough for scientists fighting Lewy body disease: a condition that up to 100,000 people in the UK live with. Further research using these models will enable us to find new drug targets. People with Lewy body disease suffer memory loss, visual hallucinations and movement difficulties. Unfortunately research is severely underfunded, and much more is needed if we are to defeat this devastating disease.â
Dr Kieran Breen, Director of Research and Development at the Parkinson's Disease Society, added: âThe formation of Lewy bodies is a key event in the development of nerve cell death associated with Parkinson's disease. Understanding how these are formed will help us to figure out what happens when nerve cells die in Parkinson's and from this to develop therapies that will ultimately provide a cure for the condition. The majority of Parkinson's research in the UK is currently funded by the Parkinson's Disease Society through voluntary donations and we hope that advances such as this will stimulate further spending on Parkinson's research.â
Depletion of 26S Proteasomes in Mouse Brain Neurons causes Neurodegeneration and Lewy-like Inclusions resembling Human Pale Bodies by R John Mayer et al is published in the August 13 edition of the Journal of Neuroscience, vol. 28, no. 32.
Here's the abstract:
http://www.jneurosci.org/cgi/content/ab ... 28/33/8189
(FYI - not available on PubMed yet)
The Journal of Neuroscience, August 13, 2008, 28(33):8189-8198
Neurobiology of Disease
Depletion of 26S Proteasomes in Mouse Brain Neurons Causes Neurodegeneration and Lewy-Like Inclusions Resembling Human Pale Bodies
Lynn Bedford,1 David Hay,1 Anny Devoy,1 Simon Paine,1 Des G. Powe,2 Rashmi Seth,2 Trevor Gray,2 Ian Topham,1 Kevin Fone,1 Nooshin Rezvani,1 Maureen Mee,1 Tim Soane,1 Robert Layfield,1 Paul W. Sheppard,3 Ted Ebendal,4 Dmitry Usoskin,5 James Lowe,2 * and R. John Mayer1 *
1School of Biomedical Sciences and 2School of Molecular Medical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom, 3BIOMOL International L.P., Exeter EX2 8NL, United Kingdom, 4Department of Neuroscience, Uppsala University, SE-751 23 Uppsala, Sweden, and 5Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-171 77 Stockholm, Sweden
Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. Here, we describe novel conditional genetic mouse models using the Cre/loxP system to spatially restrict inactivation of Psmc1 (Rpt2/S4) to neurons of either the substantia nigra or forebrain (e.g., cortex, hippocampus, and striatum). PSMC1 is an essential subunit of the 26S proteasome and Psmc1 conditional knock-out mice display 26S proteasome depletion in targeted neurons, in which the 20S proteasome is not affected. Impairment of specifically ubiquitin-mediated protein degradation caused intraneuronal Lewy-like inclusions and extensive neurodegeneration in the nigrostriatal pathway and forebrain regions. Ubiquitin and -synuclein neuropathology was evident, similar to human Lewy bodies, but interestingly, inclusion bodies contained mitochondria. We support this observation by demonstrating mitochondria in an early form of Lewy body (pale body) from Parkinson's disease patients. The results directly confirm that 26S dysfunction in neurons is involved in the pathology of neurodegenerative disease. The model demonstrates that 26S proteasomes are necessary for normal neuronal homeostasis and that 20S proteasome activity is insufficient for neuronal survival. Finally, we are providing the first reproducible genetic platform for identifying new therapeutic targets to slow or prevent neurodegeneration.