Browsing by Subject "Pathological signatures"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Publication
    Open Access
    Identification of distinct pathological signatures induced by patient-derived -synuclein structures in nonhuman primates
    (Asociación Estadounidense para el Avance de la Ciencia, 2020-05-13) Bourdenx, M.; Nioche, A.; Dovero, S.; Arotcarena, M. L.; Camus, S.; Porras, G.; Thiolat, M.L.; Rougier, N. P.; Prigent, A.; Aubert, P.; Bohic, S.; Sandt, C.; Leste-Lasserre, T.; Trigo Damas, I.; Goillandeau, M.; Perier, C.; Estrada, C.; Garcia-Carrillo, N.; Recasens, A.; Vaikath, N. N.; El-Agnaf, O. M. A.; Derkinderen, P.; Vila, M.; Obeso, J.A.; Dehay, B.; Bezard, E.; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
    Dopaminergic neuronal cell death, associated with intracellular -synuclein (-syn)–rich protein aggregates [termed “Lewy bodies” (LBs)], is a well-established characteristic of Parkinson’s disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that -syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning–based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct -syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular -syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.