Pridopidine rescues BDNF/TrkB trafficking dynamics and synapse homeostasis in a Huntington disease brain-on-a-chip model
Sophie Lenoir, Romane A. Lahaye, Hélène Vitet, Chiara Scaramuzzino, Amandine Virlogeux, Laetitia Capellano, Aurélie Genoux, Noga Gershoni‐Emek, Michal Geva, Michael R. Hayden, Frédéric Saudou
Abstract
provides a "disease-on-a-chip" platform ideal for investigating pathogenic mechanisms and drug activity. Pridopidine rescued the trafficking of BDNF and TrkB resulting in an increased neurotrophin signaling at the synapse. This increased the capacity of HD neurons to release glutamate and restored homeostasis at the corticostriatal synapse. These data suggest that pridopidine enhances the availability of corticostriatal BDNF via S1R activation, leading to neuroprotective effects.
Topics & Concepts
Tropomyosin receptor kinase BNeuroscienceHuntington's diseaseHuntingtinSynapseBrain-derived neurotrophic factorNeurotransmissionNeurotrophic factorsNeurotrophinNeuroprotectionBiologyCell biologyReceptorMedicineInternal medicineDiseaseGeneticsGenetic Neurodegenerative DiseasesNeurological disorders and treatmentsPharmacological Receptor Mechanisms and Effects