[Seminar] “Axonal transport disfunctions in neurodegenerative diseases” by Prof. Giampietro Schiavo


Thursday, March 21, 2024 - 14:00 to 15:00





Prof. Giampietro Schiavo, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London.


Axonal transport disfunctions in neurodegenerative diseases


The molecular mechanisms causing neuronal death in many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Charcot Marie Tooth (CMT) disease, are poorly understood. The key consequence of our incomplete understanding of disease pathogenesis is that there is a complete dearth of effective symptomatic treatments for these widespread global disorders, prompting the necessity for a step-change in treatment strategies to fight these pathologies.

In this view, we are investigating ALS and CMT as disease paradigms to identify new, common targets for pharmacological intervention in these devastating pathologies. Recently, we uncovered alterations in axonal transport of several cytoplasmic organelles, such as mitochondria and signalling endosomes, at pre-symptomatic stages of ALS and CMT pathogenesis, suggesting that these impairments may play a causative role in disease onset and progression. Crucially, we have restored axonal transport to physiological levels at early symptomatic stages of disease, thus demonstrating that these pathological changes are fully reversible.

In light of these promising results, our main goal is identifying novel signalling nodes that modulate axonal transport in healthy and diseased neurons. This will allow us to test the hypothesis that counteracting axonal transport deficits observed in ALS, CMT and other neurodegenerative diseases, represents a novel, effective therapeutic strategy towards treating these pathologies.


Professor Giampietro Schiavo is Deputy Director of the Queen Square Institute of Neurology, a UK Dementia Research Institute Investigator and the academic lead of the Alzheimer’s Research UK Drug Discovery Institute at UCL. He has a long-term interest in the mechanisms of action of bacterial protein toxins, in particular tetanus and botulinum neurotoxins, and their exploitation as tools in cell biology. Using these probes, his group has clarified key steps in the mechanism of ligand entry at the neuromuscular junction and other synapses, and the recruitment of ligand-receptor complexes to signalling endosomes moving along the axonal retrograde transport route. This essential transport pathway, which delivers a variety of organelles and molecular complexes to the cell body of neurons, is impaired in several nervous system pathologies, such as motor neuron disease, Alzheimer’s disease, and Charcot-Marie-Tooth disease. Professor Schiavo and his team are identifying novel pharmacological nodes to restore axonal transport of key organelles such as signalling endosomes, mitochondria, and lysosomes in neurons both in vitro and in vivo.

At the same time as maintaining an internationally competitive research output with more than 300 highly cited (>30,500; h-index 91; source: Google Scholar) peer-reviewed publications, he chaired and served on several funding committees, including ERC, MRC, ATIP/AVENIR, Wellcome Trust, MNDA, NIH. He has received several National and International Prizes such as the Giuseppe Borgia award of the Italian National Academy of Sciences, the International Society for Neurochemistry Young Scientist Award, the Giovanni Armenise-Harvard Foundation Career Development Award and the Amedeo e Frances Herlitzka Award in Physiology. He is an Editor of Journal of Cell Science and Cell Death Disease.

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