Cellular prion protein and calcium ions trigger the neurotoxicity of α-synuclein aggregates
Collectively, our findings indicate that while PrP<sup>C</sup> facilitates early events in αS aggregate interaction with neurons, the sustained neurotoxicity induced by αS prefibrillar oligomers and fibrils is predominantly mediated by extracellular Ca<sup>2+</sup>. This promotes aggregate-membrane interactions, membrane permeabilization, and intracellular Ca<sup>2+</sup> dyshomeostasis, thereby establishing a vicious cycle of neuronal dysfunction and death.
Authors
- Alessandra Bigi (ORCID: https://orcid.org/0000-0002-1067-6288)
- Fabrizio Chiti (ORCID: https://orcid.org/0000-0002-1330-1289)
- Roberta Cascella (ORCID: https://orcid.org/0000-0001-9856-6843)
- Giuliana Fusco (ORCID: https://orcid.org/0000-0002-3644-9809)
- Alfonso De Simone (ORCID: https://orcid.org/0000-0001-8789-9546)
- Cristina Cecchi (ORCID: https://orcid.org/0000-0001-8387-7737)
- A. Conti (ORCID: https://orcid.org/0000-0002-2054-7375)
- Liliana Napolitano
Institutions
- University of Cambridge (GB)
- Naples Anesthesia & Physician Associates (US)
- University of Florence (IT)
- Imperial College London (GB)
- University of Naples Federico II (IT)
Publication Details
- Journal
- Cell & Bioscience
- Published
- 2025-12-09
- DOI
- https://doi.org/10.1186/s13578-025-01479-7
- Primary Topic
- Prion Diseases and Protein Misfolding
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Università degli Studi di Firenze