Gabriele Kaminski Schierle - CNS 2023 скачать в хорошем качестве

Gabriele Kaminski Schierle - CNS 2023

About CNS2023 The 33rd annual Cambridge Neuroscience Seminar took place on Tuesday September 26th 2023 at Robinson College at the University of Cambridge. We used our annual meeting to highlight the strength in the interdisciplinary approach to tackling dementia and how collaboration, with the communal aim of understanding these diseases and identifying new treatments, is key. Exogenous Tau affects intracellular organelle morphology and neuronal signalling Abstract: The microtubule-associated protein Tau (MAPT) is implicated in various human neurodegenerative diseases. Previous research, including our own work, has established that Tau can propagate within the central nervous system, a phenomenon closely associated with the progression of Alzheimer’s disease (AD). Additionally, we have demonstrated that the uptake of monomeric Tau into cells significantly exacerbates Tau pathology3. Here, we investigated the impact of Tau uptake on organelle morphology and on neuronal signalling. We conducted organelle morphology analyses using different model systems, including mammalian COS-7 cells, primary rat cortical neurons, and human glutamatergic neurons derived from induced pluripotent stem cells (iPSCs). To study organelle topology following Tau uptake, we employed Structured Illumination Microscopy (SIM). Electrophysiology experiments were performed in rat hippocampal neurons. Our findings reveal that Tau uptake results in the collapse of the tubular endoplasmic reticulum (ER) in both COS-7 cells and human glutamatergic neurons which has significant implications for neuronal physiology and signalling. In particular, we show that the addition of Tau alone to primary hippocampal neurons do not induce a change in the evoked excitatory postsynaptic potential response, however, optogenetically induced stimulation together with Tau leads to the inhibition of the latter. Additionally, we observe a reduction and fragmentation of microtubular structures in COS-7 cells, accompanied by the clustering of enlarged lysosomes. Interestingly, lysosomal clustering has been recently shown to occur in AD patients. The synchronised defects in organelle morphology and distribution suggest a potential mechanism by which Tau uptake disrupts inter-organelle communication and homeostasis. Preliminary studies indicate that blocking Tau endocytosis can restore a healthy ER phenotype, suggesting a possible therapeutic approach against tauopathy. Biography: Cath Mummery is a consultant neurologist at the National Hospital for Neurology and Neurosurgery. She is chair of the NIHR Dementia Translational Research Collaboration, building a national unified trials network for early phase clinical trials in dementia. She is Head of Clinical Trials at the Dementia