- Prof John Hardy is the first UK winner of $3m Breakthrough Prize in Life Sciences
- John Hardy awarded 2015 Robert A. Pritzker Prize for Leadership in Parkinson's Research
- Video: Advances in Genetic Understanding of Parkinson's Disease
- GCH1 gene and Parkinson's risk
- The new Leonard Wolfson Experimental Neurology Centre (LWENC) has opened for clinical studies and trials
- LRRK2 and autophagy in fibroblasts
- LRRK2 and autophagy
- GBA and mitochondria
- Alpha-synuclein in LRRK2 brains
- α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson’s disease and multiple system atrophy?
- Video: Parkinson's and the Genetic Revolution: From Genes to Treatments
- Public lecture: The autophagy signaling network, c-‐myc and pathology: don't mess with the cell cycle!
- Video: Brain Disease Research - Keeping You You
- Video: Degenerating Brains public symposium
- Mutations in VCP gene implicated in a number of neurodegenerative diseases
- Public lectures: new research into Alzheimer's, Parkinson's and Motor Neuron Disease
- Blog: Degenerating neurons
- Global research team discovers new Alzheimer’s risk gene
- Direct Observation of the Interconversion of Normal and Toxic Forms of a-Synuclein
- Video: The genetics of LRRK2 by Nick Wood
- Video: Parkinson's UK site visit for the Targeting LRRK2 project
- Successes of Deep Brain Stimulation for patients with Parkinson's disease
- Recordings in Parkinson's disease patients reveal details of communication between deep and superficial brain structures
- Five new Parkinson's genes identified
Professor John Hardy (UCL Institute of Neurology) has been awarded the $3 million Breakthrough Prize in Life Sciences for his pioneering research into the genetic causes of Alzheimer’s disease, other forms of dementia and Parkinson’s disease. More...
One of the UK Parkinson's Disease Consortium Principal Investigators, Prof John Hardy, has been awarded the 2015 Robert A. Pritzker Prize for his leadership in Parkinson's genetics research. The award was presented by Michael J. Fox at a ceremony in New York on April 15. From the Michael J. Fox Foundation website: More...
Webcast of the presentation entitled ‘Advances in Genetic Understanding of Parkinson's Disease’ given by Nicholas Wood (University College London, United Kingdom) presented at the Biochemical Society Hot Topic event, PINK1-Parkin Signalling in Parkinson’s Disease and Beyond, held in December 2014. More...
A study published in Brain, led by researchers
at UCL Institute of Neurology, has shown that genetic mutations which
cause a decrease in dopamine
production in the brain and lead to a form of childhood-onset Dystonia,
also play a role in the development of Parkinson’s disease.
The new Leonard Wolfson Experimental Neurology Centre (LWENC) has opened for clinical studies and trials
Mutations in VCP gene implicated in a number of neurodegenerative diseases
20 March 2013
New research, published in Neuron, gives insight into how single mutations in the VCP gene cause a range of neurological conditions including a form of dementia called Inclusion Body Myopathy, Paget’s Disease of the Bone and Frontotemporal Dementia (IBMPFD), and the motor neuron disease Amyotrophic Lateral Sclerosis (ALS).
Single mutations in one gene rarely cause such different diseases. This study shows that these mutations disrupt energy production in cells shedding new light on the role of VCP in these multiple disorders.
In healthy cells VCP helps remove damaged mitochondria, the energy-producing engines of cells. The mutant protein can’t do this and as a result, the dysfunctional mitochondria build up.
The new study led by Dr Fernando Bartolome, Dr Helene Plun-Favreau and Dr Andrey Abramov of the UCL Institute of Neurology, found that mitochondria are damaged in cells from patients with mutant VCP. Mitochondria generate a cell’s energy, and the study found these damaged mitochondria are less efficient, burning more nutrients but producing less energy. This reduction in available energy makes cells more vulnerable, which could explain why mutations in the VCP gene lead to neurological disorders.
Lead author Dr Fernando Bartolome said, “We have found that VCP mutations are associated with mitochondrial dysfunction. VCP had previously been shown to be important in the removal of damaged mitochondria and proteins, accumulation of which is potentially very toxic to cells. A single mutation in the VCP gene could cause multiple neurological diseases because a different type of protein is accumulating in each disorder”.
In the study, the researchers used live imaging techniques to examine the functioning of mitochondria in patient cells carrying three independent VCP mutations, and in nerve cells in which the amount of VCP has been reduced.
“The next step will be to find small molecules able to correct the mitochondrial dysfunction in the VCP deficient cells”, added Dr Bartolome.
Dr Brian Dickie, the Motor Neuron Disease Association’s Director of Research Development says: “Neurons - and motor neurons in particular - are incredibly energy hungry cells. These new findings from the team at UCL show that there is a significant interruption of energy supply in this hereditary form of MND, which has strong implications for understanding the degenerative process underpinning all forms of the disease.”
The research was supported in part by a Wellcome Trust/MRC Joint Call
in Neurodegeneration award and by the Spanish Ministerio de Educación
through the Fundación Española para la ciencia y la tecnología (FECYT)
and grants from the ALS Association and Motor Neuron Disease (MND)
Fernando Bartolome, Hsiu-Chuan Wu, Victoria S. Burchell, Elisavet Preza, Selina Wray, Colin J. Mahoney, Nick C. Fox, Andrea Calvo, Antonio Canosa, Cristina Moglia, Jessica Mandrioli, Adriano Chiò, Richard W. Orrell, Henry Houlden, John Hardy, Andrey Y. Abramov, Helene Plun-Favreau. Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels. Neuron, 2013; DOI: 10.1016/j.neuron.2013.02.028
Page last modified on 20 mar 13 13:44