- Parkinson's chromosome deletion linked to other genetic disorders
- Prof John Hardy is the first UK winner of $3m Breakthrough Prize in Life Sciences
- John Hardy awarded 2015 Robert A. Pritzker Prize for Leadership in Parkinson's Research
- Video: Advances in Genetic Understanding of Parkinson's Disease
- GCH1 gene and Parkinson's risk
- The new Leonard Wolfson Experimental Neurology Centre (LWENC) has opened for clinical studies and trials
- 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
Researchers, led by BRC-supported Professor Nicholas Wood, UCL Institute of Neurology, have made a breakthrough in their understanding of Parkinson’s disease after they discovered a chromosome deletion linked to Parkinson’s disease and other genetic disorders. More...
Professor John Hardy (UCL Institute of Neurology) has been awarded the $3 million Breakthrough Prize in Life Sciences for his pioneering research into the genetic causes of Alzheimer’s disease, other forms of dementia and Parkinson’s disease. More...
One of the UK Parkinson's Disease Consortium Principal Investigators, Prof John Hardy, has been awarded the 2015 Robert A. Pritzker Prize for his leadership in Parkinson's genetics research. The award was presented by Michael J. Fox at a ceremony in New York on April 15. From the Michael J. Fox Foundation website: More...
Webcast of the presentation entitled ‘Advances in Genetic Understanding of Parkinson's Disease’ given by Nicholas Wood (University College London, United Kingdom) presented at the Biochemical Society Hot Topic event, PINK1-Parkin Signalling in Parkinson’s Disease and Beyond, held in December 2014. More...
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.
Alpha-synuclein in LRRK2 brains
9 July 2013
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.
A common pathological characteristic in PD patients is the abnormal
accumulation of a protein named α-synuclein that can be seen under the
microscope in neurons in the brain. This protein aggregation forms what
we call Lewy bodies, named after the prominent neurologist Dr Frederic
Lewy that characterised them in 1912. This is also followed by
α-synuclein becoming very insoluble in detergents in the lab. In fact
protein aggregation is a common pathological phenomenon seen in other
neurodegenerative diseases like Alzheimer’s disease and frontotemporal
Our goal is to understand what causes these changes in α-synuclein. In 5% of PD patients the disease is directly caused by genetic mutations that can be inherited. We hold four post-mortem PD cases from patients that carried the most prevalent mutation of the inherited form of the disease, the LRRK2 mutation G2019S. By studying these brains we found a striking difference in the insolubility properties of α-synuclein compared to brains of PD patients that did not carry mutations.
This is the first time that a difference in α-synuclein properties has been discovered between genetic and not-genetic PD and can give us clues as to the effect of the mutation in abnormal protein aggregation and neurodegeneration. Most importantly this suggests that the real detrimental effect in G2019S PD may not be caused by α-synuclein becoming insoluble while it is being deposited in Lewy bodies.
Mamais, A., Raja, M., Manzoni, C., Dihanich, S., Lees, A., Moore, D., Lewis, P., Bandopadhyay, R., 2013. Divergent a-synuclein solubility and aggregation properties in G2019S LRRK2 Parkinson’s disease brains with Lewy Body pathology compared to idiopathic cases. Neurobiol Dis.
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