RT Journal Article
T1 Amyloid-beta impairs TOM1-mediated IL-1R1 signaling
A1 Cadete Martini, Alessandra
A1 Gomez-Arboledas, Angela
A1 Forner, Stefania
A1 Rodriguez-Ortiz, Carlos
A1 McQuade, Amanda
A1 Danhash, Emma
A1 Phan, Jimmy
A1 Javoncillo, Dominic
A1 Ha, Jordan-Vu
A1 Tram, Melanie
A1 Trujillo-Estrada, Laura Isabel
A1 da Cunha, Celia
A1 Ager, Rahasson
A1 Davila, Jose Carlos
A1 Kitazawa, Masashi
A1 Blurton-Jones, Mathew
A1 Gutierrez, Antonia
A1 Baglietto-Vargas, David
A1 Medeiros, Rodrigo
A1 LaFerla, Frank M
K1 Alzheimer, Enfermedad de
AB Defects in interleukin-1β (IL-1β)-mediated cellular responses contribute to Alzheimer's disease (AD). To decipher the mechanism associated with its pathogenesis, we investigated the molecular events associated with the termination of IL-1β inflammatory responses by focusing on the role played by the target of Myb1 (TOM1), a negative regulator of the interleukin-1β receptor-1 (IL-1R1). We first show that TOM1 steady-state levels are reduced in human AD hippocampi and in the brain of an AD mouse model versus respective controls. Experimentally reducing TOM1 affected microglia activity, substantially increased amyloid-beta levels, and impaired cognition, whereas enhancing its levels was therapeutic. These data show that reparation of the TOM1-signaling pathway represents a therapeutic target for brain inflammatory disorders such as AD. A better understanding of the age-related changes in the immune system will allow us to craft therapies to limit detrimental aspects of inflammation, with the broader purpose of sharply reducing the number of people afflicted by AD.
PB National Academy of Sciences
YR 2019
FD 2019-10
LK https://hdl.handle.net/10630/33778
UL https://hdl.handle.net/10630/33778
LA eng
NO Alessandra Cadete Martini, Angela Gomez-Arboledas, Stefania Forner, Carlos J. Rodriguez-Ortiz, Amanda McQuade, Emma Danhash, Jimmy Phan, Dominic Javonillo, Jordan-Vu Ha, Melanie Tram, Laura Trujillo-Estrada, Celia da Cunha, Rahasson R. Ager, Jose C. Davila, Masashi Kitazawa, Mathew Blurton-Jones, Antonia Gutierrez, David Baglietto-Vargas, Rodrigo Medeiros, and Frank M. LaFerla. Amyloid-beta impairs TOM1-mediated IL-1R1 signaling
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 22 ene 2026