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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...

α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson’s disease and multiple system atrophy?

21 June 2013

Immunofluorescent image showing a-synuclein in green.

a-Synucleinopathies share the common feature of depositions of a-synuclein protein in cells of the brain. In Parkinson’s disease (PD) these deposits occur in neurons or their processes and are known as Lewy bodies or Lewy neurites respectively. While the hallmark feature of Multiple System Atrophy (MSA) is the localisation of a-synuclein within oligodendrocytes, which is known as glial cytoplasmic inclusions (GCIs).

Interestingly, although several mutations of the SNCA gene, which encodes the a-synuclein protein, have been found to cause PD, none have yet been identified in MSA.

This report describes the unusual clinical progression and neuropathological features in a family in which carriers of a G51D mutation of the SNCA gene develop young onset parkinsonism. The neuropathology observed in the deceased family member described here, is particularly fascinating as it shares both the cellular pathology of Parkinsonism such as the characteristic features of cell loss, a-synuclein accumulation within neurons and the distinctive GCIs of MSA. In addition a-synuclein inclusions in both cell types were abundant and widespread affecting both areas typically associated with PD and MSA and those which are generally less affected such as the striatum and both the superior and deep cortical layers. This pathology of combined cellular features of PD and MSA appears to be similar to cases reported which have A53T SNCA mutation and multiplication of the SNCA gene.

This could suggest that, like in cases of over production of a-synuclein, cases with mutations in this region of the protein could have the ability to accumulate in and/or not be cleared from, greater numbers of cells and cell types. For this reason the data described in this paper provides us with interesting insight in the mechanisms which result in the distinct pathologies of both PD and MSA.

Contributed by Dr Aoife Kiely.

Kiely, A., Asi, Y., Kara, E., Limousin, P., Ling, H., Lewis, P., Proukakis, C., Quinn, N., Lees, A., Hardy, J., Revesz, T., Houlden, H., Holton, J., 2013. a-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy? Acta Neuropathol 125, 753–769.

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