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...

Image of alpha-synuclein

Alpha-synuclein in LRRK2 brains

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...

Parkinsonism and Lysosomal Storage Disorders share etiology

5 March 2012

There are several genes in which we now know that mutations cause Parkinson's disease (PD). These range from fairly frequent mutations, like those in LRRK2, to rarer ones such as those in SNCA.

One of the rare genes is ATP13A2, known to cause Kufor-Rakeb syndrome (KRS), a form of autosomal recessive hereditary parkinsonism with dementia and juvenile onset. Although little is known about the function of this gene, it is suspected to act in the lysosomal membrane, and to be responsible for the maintenance of lysosomal pH. The lysosomal pathway has, in the last few years, attracted interest as a novel mechanism involved in the pathogenesis of PD, following not only the identification of ATP13A2 mutations, but also the risk conferred by GBA mutations for the development of this disorder.

A team of researchers led by Drs. Rita Guerreiro and Jose Bras at UCL has identified mutations in ATP13A2 as a cause of a separate disease entity called Neuronal Ceroid-Lipofuscinosis (NCL) in a large family from Belgium.

Figure: Identification of a homozygous mutation in ATP13A2

Figure: Identification of a homozygous mutation in ATP13A2.

NCLs are a clinically and genetically heterogeneous group of neurodegenerative disorders, characterized by the intracellular accumulation of autofluorescent lipopigment storage material. It is well known that the lysosome plays a pivotal role in these disorders.

These results show undisputable evidence that the lysosomal pathway plays a role in the pathogenesis of parkinsonian phenotypes and further suggest that KRS and NCL may share pathobiological features.


Mutation of the Parkinsonism Gene ATP13A2 Causes Neuronal Ceroid-Lipofuscinosis, Hum. Mol. Genet., 2 March 2012, doi: 10.1093/hmg/dds089

Rita Guerreiro's profile

Jose Bras' profile

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