- LRRK2 and autophagy in fibroblasts
- LRRK2 and autophagy
- GBA and mitochondria
- Alpha-synuclein in LRRK2 brains
- α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson’s disease and multiple system atrophy?
- Video: Parkinson's and the Genetic Revolution: From Genes to Treatments
- Public lecture: The autophagy signaling network, c-‐myc and pathology: don't mess with the cell cycle!
- Video: Brain Disease Research - Keeping You You
- Video: Degenerating Brains public symposium
- Mutations in VCP gene implicated in a number of neurodegenerative diseases
- Public lectures: new research into Alzheimer's, Parkinson's and Motor Neuron Disease
- Blog: Degenerating neurons
- Global research team discovers new Alzheimer’s risk gene
- Direct Observation of the Interconversion of Normal and Toxic Forms of a-Synuclein
- Video: The genetics of LRRK2 by Nick Wood
- Video: Parkinson's UK site visit for the Targeting LRRK2 project
- Successes of Deep Brain Stimulation for patients with Parkinson's disease
- Recordings in Parkinson's disease patients reveal details of communication between deep and superficial brain structures
- Five new Parkinson's genes identified
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...
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...
First author Adamantios Mamais tells us about his recent publication in Neurobiology of Disease: At the Queen Square Brain Bank (part of the UCL Institute of Neurology) we hold a large collection of post-mortem human brain tissue from patients with neurodegenerative diseases including Parkinson’s disease (PD); a debilitating neurological disorder that affects the central nervous system. In the United States alone about 50,000 new cases are reported every year. The main symptoms include tremor, slow movement, rigid limbs and a shuffling gait while these worsen with time. More...
α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson’s disease and multiple system atrophy?
21 June 2013
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).
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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