Innovative treatment targeting gangliosides aimed at blocking the formation of neurotoxic alpha-synuclein oligomers in Parkinson's disease

Nouara Yahi (1) , Coralie Scala (2) , Henri Chahinian (1) , Jacques Fantini (1)

1 UNIS - Inserm U1072 - Unité de Neurobiologie des canaux Ioniques et de la Synapse
2 Helsingin yliopisto = Helsingfors universitet = University of Helsinki

Current therapeutic strategies are centered on the dopaminergic system, with limited efficacy, so that a treatment that has a direct impact on the underlying disease pathogenesis is urgently needed.-synuclein is a privileged target for such therapies, this protein has been in the past wrongly considered as exclusively intracellular, so that the impact of paracrine neurotoxicity mechanisms in PD have been largely ignored. In this article we review the data showing that lipid rafts act as plasma membrane machineries for the formation of-synuclein pore-like oligomers which trigger an increase of intracellular Ca 2+. This Ca 2+ influx is responsible for a self-sustained cascade of neurotoxic events, including mitochondrial oxidative stress, tau phosphorylation, Ca 2+ release from the

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology

Nouara Yahi, Coralie Scala, Henri Chahinian, Jacques Fantini. Innovative treatment targeting gangliosides aimed at blocking the formation of neurotoxic alpha-synuclein oligomers in Parkinson's disease. Glycoconjugate Journal, 2021. ⟨hal-03600650⟩