Patients diagnosed with Parkinson’s disease contain distinct, characteristic structures called “Lewy bodies” in their brains, structures which are still not fully explored today and demand further research, specifically, how they first develop in neurons and what exactly they’re made of and how they contribute to the initiation or progression of the disease.
So far, Lewy bodies have been marked as prime targets for developing therapies and diagnostics for Parkinson’s and related diseases, but the absence of experimental models that reproduce all the stages of Lewy Body formation and maturation limits our understanding of the different processes involved the pathogenesis of Parkinson’s disease.
But now, in a new paper published in PNAS, researchers from EPFL’s Brain Mind Institute describe a neuronal model that reproduces the key events leading to the formation of inclusions that recapitulate the biochemical, structural, and organisational features of bona fide LBs. To that end, EPFL scientists have carried out the first study to track the development of alpha-synuclein Lewy bodies from beginning to end. Using an integrative omics, biochemical and imaging approach, they have dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration.
The extensive study, led by the group of Hilal Lashuel at EPFL, provides new insights into the composition and mechanisms of Lewy body formation, and shows that the process of Lewy body formation, as opposed to simply fibrillisation, is one of the main drivers for neurodegeneration.
“Our results generally agree with recent findings reported on Lewy bodies from Parkinson’s disease brains,” says Hilal Lashuel. “But while previous studies only offered snapshots of fibril evolution, our model can reconstruct the entire process of Lewy body formation, making it a powerful platform for elucidating the relationship between fibrillization and neurodegeneration in Parkinson’s and other diseases, and to screen for novel potentially disease modifying therapies.”