Mechanism of spreading of prion and polyglutamine aggregates and role of the cellular prion protein in Huntington’s disease
type: Dataset
description: The pathogenesis of most neurodegenerative diseases, including transmissible diseases like prion encephalopathies, inherited disorders like Huntington’s disease, and sporadic diseases like Alzheimer’s and Parkinson’s diseases, appear to be directly linked to the formation of fibrillar protein aggregates. For many years, the concept of aggregate spreading and infectivity has been confined to prion diseases. However, recent evidence indicate that both extracellular (e.g. amyloid-β) and intracellular (α- synuclein, tau, huntingtin) amyloidogenic protein are able to move (and possibly replicate) within the brains of affected individuals, thereby contributing to the spread of pathology in a prion-like manner (Brundin et al., 2010; Jucker and Walker, 2011; Aguzzi and Rajendran, 2009). Recently another intriguing connection has been made between prions and other aggregation proteinopathies, as it was suggested that the cellular prion protein, PrPC, whose pathological counterpart is responsible for prion diseases, possibly mediates the toxicity of Aβ, the pathogenic protein in Alzheimer’s disease, and of other β- conformers independently of the propagation of infectious prions (reviewed in Biasini et al., 2012). However, despite the intense research, many questions in prion and non-prion neurodegenerative diseases are still open regarding both the mechanism of protein aggregate spreading and the mechanism of toxicity. In the first part of my thesis, I contributed to investigate the role of DCs (dendritic cells) in the spreading of prion infection to neuronal cells. I demonstrated that the transfer of PrPSc from DCs (loaded with prion infected brain homogenate) to primary neurons was triggered by direct cell–cell contact and resulted in transmission of infectivity to the co-cultured neurons. These data confirm the possible role of DCs in prion spreading from the periphery to the nervous system. I also provided a plausible transfer mechanism of PrPSc through tunneling nanotub…
identifier: NNT: 2012PA112186
issued: 2026-05-10T22:01:11.326726
language: en
modified: 2026-05-10T22:01:11.326730
contact point: Organization
  fn: CCSD
keyword: agregats-polyglutaminiques
keyword: huntingtons-disease
keyword: infoeu-reposemanticsdoctoralthesis
keyword: intercellular-transfer
keyword: maladie-de-huntington
keyword: nanotubes-tnts
keyword: polyglutamine-aggregates
keyword: prion
keyword: protein-misfolding
keyword: proteine-malformee
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: theses
keyword: transfert-intercellulaire
keyword: tunneling-nanotubes-tnts
landing page: https://theses.hal.science/tel-00829104

Mechanism of spreading of prion and polyglutamine aggregates and role of the cellular prion protein in Huntington’s disease
type: Distribution
format: HTML
issued: 2026-05-10T22:01:11.340999
modified: 2026-05-10T22:01:11.305670
access URL: https://theses.hal.science/tel-00829104

test_moissonnage_selune
type: Agent