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Leonard Wolfson Experimental Neurology Centre (LWENC)

The new Leonard Wolfson Experimental Neurology Centre (LWENC) has opened for clinical studies and trials

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Audioslide presentation on Claudia Manzoni's paper examining how fibroblasts with LRRK2 mutations react to starvation conditions and the possible deficits that they have in autophagy.

LRRK2 and autophagy in fibroblasts

In this paper Claudia Manzoni studies how fibroblast cells from people with Parkinson’s disease caused by mutations in LRRK2 react to starvation. Although the changes are quite subtle, there are differences between the way that fibroblasts that contain mutant LRRK2 respond to being starved – suggesting that there may be changes in the way that these cells regulate a key process called autophagy (a term which comes from the greek meaning to eat yourself, and is one of the ways that cells get rid of waste and recycle proteins and organellles).
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Drosophila fly model - University of Sheffield

Genetic mutations linked to Parkinson's disease

Research led by consortium researchers Dr Helene Plun-Favreau (UCL Institute of Neurology) and Dr Alex Whitworth (University of Sheffield), and collaborator Dr Heike Laman (University of Cambridge), has discovered how genetic mutations linked to Parkinson’s disease might play a key role in the death of brain cells, potentially paving the way for the development of more effective drug treatments. In the new study, published in Nature Neuroscience, the team of cross-institutional researchers showed how defects in the Parkinson’s gene Fbxo7 cause problems with mitophagy. More...

Autophagy

LRRK2 and autophagy

Mutations in LRRK2 are the most common genetic cause of Parkinson’s disease. Here, Claudia Manzoni talks about her research (funded by the Rosetrees Trust and the Michael J. Fox Foundation) into what LRRK2 might be doing within the cell: Parkinson’s disease is a brain illness that afflicts 1 in 500 people in the UK. High profile patients, such as the actor Michael J Fox, the boxer Muhammad Ali and the late Pope John Paul II, have raised public awareness of Parkinson’s and its devastating impact. More...

GBA neurons

GBA and mitochondria

Dr Laura Osellame tells us about her recent paper in Cell Metabolism about Mitochondrial dysfunction linked to loss of an enzyme called GBA: Gaucher Disease (GD) is a rare inherited disease, belonging to the family of lysosomal storage disorders. Mutations in the gene glucocerebrosidase (GBA) are responsible for the disease and can increase susceptibility to Parkinson’s disease (PD). Genetic studies undertaken at UCL and other hospitals around the world suggest that mutations in GBA are the most common genetic risk factor currently known for PD. More...

Background

Understanding Parkinson`s Disease: Lessons from Biology

Parkinson's disease is a common neurodegenerative disease that afflicts more than 2 per cent of people aged over 75 years. In the UK, this means there are over 100 000 people with the disease: with the ageing population this number will increase. The annual cost in nursing-home care for Parkinson's disease alone in the UK is estimated to be about £600-800 million.

Despite tremendous progress in the identification of genes associated with Parkinson’s and related disorders over the last decade, there is still only outline and sketchy information about the molecular pathways involved, and their constituents and their interactions.

Finally, in order to really understand the pathway to human disease, and to be able to influence its progression, the earliest phase needs to be examined. Thus the consortium will also focus on developing understanding of the very early symptoms or warnings of the illness.

The consortium hypothesises that there are multiple causes of Parkinson's, which result in a very small number of separate but converging biochemical pathways. These pathways interact with the molecular pathology of ageing and induce neuronal dysfunction and death, producing the characteristic pathological features of the condition.

It will need to identify all the significant genetic risk factors, and place these molecules and their variants in their pathways to enable it to understand how the human disease begins and develops.

To understand these pathways and mechanisms requires the establishment and integrated use of a range of models.

The consortium aims to achieve a much fuller picture of all the major genetic factors that underlie Parkinson's. It will then identify and characterise the biochemical pathways that these genes determine, and explore their role in the development of disease. To dissect these mechanisms, the consortium has brought in expertise from mitochondrial biology, cell signalling and Drosophila biology to complement its other model systems.

In parallel it will study the very earliest stages of the illness. It is widely believed that only by understanding these early phases will we be able to modify the disease course for the greatest clinical impact. To aid this work, the consortium has harnessed the clinical and biochemical resources of the national Gaucher's disease clinic. This will help it to build cohorts of individuals who are genetically at risk; detailed studies of these individuals will include imaging and biochemical assessments.

Over the next five years, the consortium’s plan is to produce detailed knowledge of the molecular pathways that lead to Parkinson’s, and validated markers of its evolution.

Page last modified on 08 feb 11 12:30