

LRRK2 and autophagy in fibroblasts


Drosophila fly model - University of Sheffield

Genetic mutations linked to Parkinson's disease



LRRK2 and autophagy


GBA neurons

GBA and mitochondria


Image of alpha-synuclein

Alpha-synuclein in LRRK2 brains



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