Event

Lecture Series on Neurodegeneration – Tubes, Channels and Iron: Intercellular Connectivity, Glymphatic Clearance and Iron Accumulation in Parkinson’s Disease

  • Conférencier  Dr Dean Pountney

  • Lieu

    BT2 – RIKEN room (ground floor)

    6 avenue du Swing

    4367, belvaux, LU

Dr Pountney leads the Neurodegeneration Research Group at Griffith University, Australia, with a focus on investigating potential therapeutic targets of Parkinson’s and atypical Parkinson’s diseases. After studying in London and Norwich, UK, he did post-doctoral work in Zurich, Minnesota and Adelaide on metallothionein and zinc-finger proteins, before establishing an independent lab in Queensland. His major contributions are in the role of metallothionein, calcium and copper in neurodegeneration, the SUMO post-translational modification pathway, α-synuclein and neuroinflammation.

Talk abstract

Parkinson’s disease, Multiple System Atrophy (MSA), and Dementia with Lewy Bodies (DLB) comprise a group of neurodegenerative diseases termed α-synucleinopathies characterized by the abnormal aggregation of the protein α-synuclein in the CNS. We are investigating multiple α-synuclein pathogenic mechanisms that may reveal novel therapeutic targets, including intercellular connectivity, glymphatic clearance and iron accumulation. Tunneling nanotubes (TNTs) are an emerging route of long-range intercellular communication that mediate cell-to-cell exchange of cargo and organelles and contribute to maintaining cellular homeostasis by balancing diverse cellular stresses. Besides their role in intercellular communication, TNTs are implicated in neurodegenerative diseases. We reported previously that α-synuclein aggregates can move from cell to cell via TNTs bound to mitochondria. Currently, we find that α-synuclein aggregates can also promote TNT formation, which could thereby increase TNT-mediated spread of α-synuclein pathology within the brain. The glymphatic system is a glial-dependent perivascular network which promotes the clearance of interstitial waste in the CNS. CSF is unidirectionally transported along periarterial spaces bounded by astrocytic end-foot processes expressing aquaporin-4 channels and movement of CSF drives ISF flux, facilitating drainage of interstitial solutes and CSF-ISF fluid into the perivenous space, which is ultimately cleared from the brain. Immunofluorescence studies of MSA and DLB tissue shows reduced AQP-4 coverage of blood vessels compared to normals and α-synuclein aggregates were also found to reduce AQP-4 polarization to end-foot-like structures in cell culture, suggesting a direct link between α-synuclein aggregates and glymphatic dysfunction. Iron is enriched in PD brain tissue in both glial cells and neurons and α-synuclein aggregates have been shown to impair autophagy pathways, including ferritinophagy, which is required to release iron from intracellular ferritin stores. We found that inducing α-synuclein aggregation in cell culture models resulted in ferritin-accumulation and demonstrated that inhibition of the post-transitional modifier, SUMO, a ubiquitin homologue which promotes autophagy can promote ferritin clearance consistent with increased ferritinophagy.

Prior to this lecture Prof Mark H. Ellisman will give a talk on “Probes, Instruments and Algorithms to Propel Multiscale-Multimodal Imaging Investigations of the Brain in Health and Disease”  as part of the lecture series “Next-Generation of Multi-Omics Research: Going to the single cell. Infection and Immunity”. Mark Ellisman’s presentation will take place Prior to this lecture Prof Mark H. Ellisman will give a talk on “Probes, Instruments and Algorithms to Propel Multiscale-Multimodal Imaging Investigations of the Brain in Health and Disease”  as part of the lecture series “Next-Generation of Multi-Omics Research: Going to the single cell. Infection and Immunity”. Mark Ellisman’s presentation will take place Prior to this lecture Prof Mark H. Ellisman will give a talk on “Probes, Instruments and Algorithms to Propel Multiscale-Multimodal Imaging Investigations of the Brain in Health and Disease” “Probes, Instruments and Algorithms to Propel Multiscale-Multimodal Imaging Investigations of the Brain in Health and Disease”  as part of the lecture series “Next-Generation of Multi-Omics Research: Going to the single cell. Infection and Immunity”. Mark Ellisman’s presentation will take place “Probes, Instruments and Algorithms to Propel Multiscale-Multimodal Imaging Investigations of the Brain in Health and Disease” Prior to this lecture Prof Mark H. Ellisman will give a talk on  as part of the lecture series “Next-Generation of Multi-Omics Research: Going to the single cell. Infection and Immunity”. Mark Ellisman’s presentation will take place 

We highly encourage PhD candidates and postdocs to join the ‘meet the speaker’ session after the talk from 12 to 1 PM. Please register by email to cathia.rausch@uni.lu

For more information about Mark Ellisman’s presentation, please click here.