I.Benilova@prion.ucl.ac.uk • PubMed • Publons |
Research Synopsis
Prion disease is a fatal transmissible neurodegenerative disease characterized by cerebral deposition of misfolded prion protein and neuronal loss. Studies in wild type and transgenic mouse models of prion disease suggest that prion propagation in brain involves two distinct phases. We hypothesize that once prion propagation saturates there is a mechanistic switch from autocatalytic production of infectivity to a toxic pathway where prions act as a catalytic surface for the production of toxic species. In Parmjit Jat’s group, we are developing multiparametric cell-based assays to investigate the precise temporal relationship between infectivity and toxicity in a mouse model of scrapie.
Selected Publications
Highly infectious prions are not directly neurotoxic
Benilova, I.,* Reilly, M.*, Terry, C., Wenborn, A., Schmidt, C., Marinho, A., Risse, E., Al-Doujaily, H., Wiggins De Oliveira, M., Sandberg, M., Wadsworth, J., Jat, P., Collinge, J. (2020) PNAS 117 (38), 23815-23822. * denotes equal contribution
Mixing Aβ(1–40) and Aβ(1–42) peptides generates unique amyloid fibrils
Cerofolini, L., Ravera, E., Bologna, S., Wiglenda, T., Boddrich, A., Purfurst, B., Benilova, I., Korsak, M., Gallo, G., Rizzo, D., Gonnelli, L., Fragai, M., De Strooper, B., Wanker, E., Luchinat, C. (2020) Chem Comm 56, 8830-8833.
A new cell model for investigating prion strain selection and adaptation
Philiastides, A., Ribes, J.M., Yip, D.C., Schmidt, C., Benilova, I., Klohn P.K. (2019) Viruses 11 (10), 888.
The Alzheimer Disease Protective Mutation Ala2Thr Modulates Kinetic and Thermodynamic Properties of Abeta Aggregation
Benilova, I., Gallardo, R., Ungureanu, A. A., Castillo Cano, V., Snellinx, A., Ramakers, M., Bartic, C., Rousseau, F., Schymkowitz, J., and De Strooper, B. (2014) JBC 289, 30977–30989.
The toxic Abeta oligomer and Alzheimer's disease: an emperor in need of clothes
Benilova, I., Karran, E., and De Strooper, B. (2012) Nature Neuroscience 15, 349-357