Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson’s disease - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue (Data Paper) Journal of Experimental Medicine Année : 2016

Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson’s disease

Résumé

Parkinson’s disease (PD) is characterized by the progressive appearance of intraneuronal Lewy aggregates, which are primarily composed of misfolded α-synuclein (α-syn). The aggregates are believed to propagate via neural pathways following a stereotypical pattern, starting in the olfactory bulb (OB) and gut. We hypothesized that injection of fibrillar α-syn into the OB of wild-type mice would recreate the sequential progression of Lewy-like pathology, while triggering olfactory deficits. We demonstrate that injected α-syn fibrils recruit endogenous α-syn into pathological aggregates that spread transneuronally over several months, initially in the olfactory network and later in distant brain regions. The seeded inclusions contain posttranslationally modified α-syn that is Thioflavin S positive, indicative of amyloid fibrils. The spreading α-syn pathology induces progressive and specific olfactory deficits. Thus, we demonstrate that propagating α-syn pathology triggered in the OB is functionally detrimental. Collectively, we have created a mouse model of prodromal PD.

Dates et versions

hal-04247749 , version 1 (18-10-2023)

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Nolwen L. Rey, Jennifer Steiner, Nazia Maroof, Kelvin Luk, Zachary Madaj, et al.. Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson’s disease. Journal of Experimental Medicine, 2016, 213 (9), pp.1759-1778. ⟨10.1084/jem.20160368⟩. ⟨hal-04247749⟩
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