Are peripheral and CNS inflammation drivers of neurodegeneration

Are peripheral and CNS inflammation drivers of neurodegeneration
Theme: Parkinson's disease and other neurodegenerative disorders

Part of the Parkinson’s UK Programme Stream
Monday 24th April, 15:30 – 17:10

The classical pathology of Parkinson's, namely loss of nigrostriatal dopaminergic neurons and the presence of alpha-synuclein containing aggregates, is also associated with a chronic neuroinflammatory response. Post-mortem studies of Parkinson's patients and in animal models of Parkinson's demonstrate increased activation of glial cells and increased release of pro-inflammatory factors in key areas of the brain demonstrating pathology. Furthermore PET brain imaging studies utilizing markers of microglial activation have revealed increased neuroinflammation even in prodromal cases of Parkinson's. Additionally, the peripheral immune system is also implicated in the pathogenesis of Parkinson's. Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of Parkinson's patients. Interestingly, inflammatory responses in the gut have been hypothesized as the origins of Parkinson's where alpha-synuclein, the protein associated with Parkinson's pathology, first misfolds and these abnormal proteins are transmitted to the brain via the vagus nerve. However, inflammatory changes are common to a number of neurodegenerative conditions, so are these inflammatory changes drivers of pathology or are they simply a consequence of the neurodegenerative process? This symposium will examine the different arms of the inflammation process in Parkinson's, and the cell types which drive it, and assess the evidence for the potential damaging effects of neuroinflammation and whether this is a potential drug target for therapies to slow Parkinson's.

 Deborah Kronenberg- Versteeg, University of Tubingen, Germany: New models to investigate the role of microglia in Parkinson’s disease

Biography: Deborah and her team are particularly interested in neuron-glial interactions in the context of ageing
and neurodegeneration. Deborah’s enthusiasm for (micro)glial biology developed during a journey
through various research fields, from obtaining a masters degree in Clinical Epidemiology in
Rotterdam, to a PhD in Immunology from King's College London, postdoctoral training at the
Wellcome-MRC Cambridge Stem Cell Institute, to the Hertie Insititute for Clinical Brain Research and
the DZNE in Tübingen, Germany, where she is based now. Deborah is passionate about science,
equality, and sourdough.

 Ian Harrison, University College London, UK: Exploring the therapeutic potential of the glymphatic system in the clearance of pathological alpha-synuclein from the brain (co-chair)

Biography: Ian Harrison is a Senior Research Fellow at University College London’s Centre for Advanced Biomedical Imaging, funded by joint fellowship awards from Alzheimer’s Research UK and Parkinson’s UK. His research is focussed on understanding the involvement of the glymphatic system in neurodegenerative disease. He graduated from the University of Southampton in 2009 with his BSc in Pharmacology before continuing his postgraduate training at Imperial College London, completing his PhD in neuropharmacology under the supervision of Prof David Dexter. He joined UCL in 2014 as a postdoctoral researcher before establishing his own group in 2019. 

 Soyon Hong, University College London, UK: Neuroimmune mechanisms along the gut-brain axis in synucleinopathy models

Biography: Dr Soyon Hong is a Group Leader at the UK Dementia Research Institute (UK DRI) at University College London (UCL). She received her PhD in Neuroscience in 2012 from Harvard University, after having trained with Dr Dennis Selkoe, and completed her post-doctoral fellowship at Boston Children’s Hospital and Harvard Medical School in 2018 in the lab of Dr Beth Stevens. While in this latter role, she conducted a study that was among the first to propose microglia as critical players in synaptic pathology in disease. In 2018, Dr Hong started her lab at the UK DRI, aiming to understand immune mechanisms of neural circuitry and function. Specifically, the lab studies how synapses are targeted in the adult brain for elimination. To that end, the lab recently discovered a role for perivascular cells in influencing microglia-synapse phagocytosis via SPP1/osteopontin in models of amyloidosis. The lab employs spatial and single-cell omics as well as functional studies in disease models to profile intercellular neuroimmune/neuroglial interactions and how they may confer region-specific neuronal and synaptic vulnerability in Alzheimer’s and Parkinson’s diseases.

 Caroline Williams-Gray, Cambridge University, UK: The peripheral immune system: a new therapeutic target in Parkinson's disease (co-chair)

Biography: Caroline Williams-Gray is a Principal Research Associate in the Department of Clinical Neurosciences, University of Cambridge, and an honorary consultant neurologist specializing in Parkinson’s disease and movement disorders. She leads a translational research group investigating the clinical and biological heterogeneity of PD, with the ultimate goal of developing more targeted therapies for different Parkinson’s subtypes. Her recent work has focused on the theory that the immune system plays a significant role in mediating the heterogeneity of PD and its progression. Her lab is investigating this using blood and CSF-based immune markers, PET neuroimaging and neuropathology in stratified PD cohorts; and she is leading the first randomized controlled trial repurposing a peripheral immunosuppressive drug (azathioprine) to slow the progression of PD. 

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