Leonard Wolfson Experimental Neurology Centre (LWENC)

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


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).

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...


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...

Molecular Neuropathology Group

Our current research focuses on understanding the normal biology and pathogenic properties of key molecules associated with familial forms of PD like LRRK2 and alpha-synuclein using our unique post-mortem human brain tissue resource at the Queen Square Brain Bank. We use a variety of approaches including cellular, immunohistochemical and biochemical techniques to understand the role of key proteins in PD pathogenesis. We hypothesize that LRRK2 can function as a protein kinase in vivo and that phosphorylation of certain key substrates is critical for mediating the downstream toxic properties of LRRK2 in neurodegeneration. Therefore one of our aims is to identify and validate in vivo phosphorylation targets of LRRK2 from our G2019S mutation cases.

In addition we are also investigating a possible role of LRRK2 in mRNA processes following up on recent publications that link this protein to mechanisms of translational control. We are focusing on the dynamics/function of the cytoplasmic RNA processing bodies called stress granules, that have been recently linked to pathogenic protein aggregation in neurodegeneration. We are utilising the LRRK2-IN-1 kinase inhibitor and LRRK2 constructs carrying disease-linked mutations to examine a role of the kinase activity in the subcellular localisation of LRRK2 under cellular stress.

Other aspects of our research are to investigate i) the properties of various alpha-synuclein alternatively spliced isoforms and ii) whether glucose metabolism is dysfunctional in PD.

Lewy bodies (black arrows) and Lewy neurites (white arrows) positive for phospho-alpha synuclein in a PD case. A) substantia nigra and B) cortex (cingulate gyrus).

Figure 1: Lewy bodies (black arrows) and Lewy neurites (white arrows) positive for phospho-alpha synuclein in a PD case. A) substantia nigra and B) cortex (cingulate gyrus).

Lab website

Page last modified on 04 apr 11 10:00