Block LRRK2, increase autophagy?

For the past few years, Claudia Manzoni in the lab has been investigating what pathways LRRK2 links to in the cell. Using different inhibitors of LRRK2 kinase activity, she has discovered that blocking this aspect of LRRK2 biology causes an increase in a cellular process called autophagy – one of the ways that cells dispose of or recycle waste. Although we don’t yet know exactly how LRRK2 is regulating this process, this is a very interesting observation, especially in the context of an increasing awareness of the role that autophagy might be playing in Parkinson’s (see our earlier post on this). You can read all about the experiments we did online in Claudias paper:

The 5th meeting on advances in molecular mechanisms underlying neurological disorders

The 5th meeting on advances in molecular mechanisms underlying neurological disorders, co-organised by the Biochemical Society and the European Society for Neurochemistry, Three days of lectures, symposiums and workshops

David Attwood (UCL) kicked off the meeting with a plenary lecture on his fascinating studies of astrocyte biology. This was followed by a lovely reception at the Roman baths down in the centre of town.

The first major session was devoted to autophagy and its role in neurodegeneration, with some excellent talks from David Rubinsztein (Cambridge) and Ana Marie Cuervo (Albert Einstein College of Medicine) amongst others. This is a hot topic in neurodegeneration at the moment, and from the data presented at this meeting (including some very elegant work from Dr Cuervo on chaperone mediated autophagy and LRRK2) there is a lot more to come.

Another hot topic is stem cell models for disease, and in particular induced pluripotent stem cell models. Another session was given over to iPSC models, with excellent presentations from Tilo Kunath (Edinburgh), Richard Wade Martins (Oxford) and Larry Goldstein (UCSD) underlining the power of this approach – recreating brain disease in a dish.

Alpha synuclein is a particular interest of mine (as witnessed by some of my earlier blog posts), and an excellent session on Monday afternoon provided a host of detailed biochemical analyses from Jennifer Lee (NIH), who talked about the interaction between synuclein and GBA, and David Brown (Bath) discussing whether synuclein forms a tetramer or not. Fascinating stuff.

A highlight of the meeting was the award of two prize lectures. Joseph Kittler, from the UCL department of Neuroscience, Physiology and Pharmacology, was awarded the ESN young investigator awards and gave a fascinating account of his laboratories work on the control of mitochondrial health and location within cells. This was followed by Michael Ehlers (Pfizer), who described his pioneering work on dendritic transport and received the Thudichum Medal from the Biochemical society.

Unfortunately I missed the RNA in neurodegenerative disease session (due to an unavoidable meeting back in London), but by all accounts Jernej Ule – who has just joined the Department of Molecular Neuroscience at the Institute of Neurology – gave an excellent talk on his work looking at RNA networks. Chris Shaw from Kings talked about his work on ALS.

This was followed by a mini symposium on oxidative stress, with Michael Duchen (UCL) and Pam Shaw (Sheffield) talking about their work on mitochondrial biology and motor neuron disease respectively.

The meeting closed with a symposium on protein trafficking in health and disease. A fascinating talk from Casper Hoogenraad (Utrecht) really set the stage for a great set of talks, including one of huge interest to me from Kurt de Vos (Sheffield) presenting data on LRRK2 and its possible role in axonal transport.

All in all a great meeting, with some really world class speakers.