UK Parkinson's Disease Consortium - UKPDC
- Principal Investigators
- Research Groups
- Cell Physiology
- Clinical Neuroscience
- Clinical Studies
- Drosophila Genetics
- Molecular Biology and Biochemistry
- Molecular Neuropathology
- Neurological Biochemistry
- Neurological Signalling
- Protein Phosphorylation
- Contact us
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
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).
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...
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...
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.
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).
Page last modified on 04 apr 11 10:00