McManus laboratory

Innate immunity in neurodegenerative disease

Project details

Our previous studies have shown an important role for the NLRP3 inflammasome in the development of Alzheimer’s disease and other conditions such as Frontotemporal dementia. As part of this work, we have developed a novel way to prevent NLRP3 signaling using targeted antisense oligonucleotides (ASOs) and we have uncovered a new role for NLRP3 in regulating microglial phagocytic activity. We now focus on strategies to understand the precise mechanism of inflammasome activation in microglia and the implications for cellular function.

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Project-related publications

NLRP3 inflammasome signalling in Alzheimer's disease

Róisín M. McManus and Eicke Latz

Neuropharmacology 2024 Mar 31:252:109941

NLRP3-directed antisense oligonucleotides reduce microglial immunoactivities in vitro

Charlotte Braatz, Max P. Komes, Kishore Aravind Ravichandran, Matheus Garcia de Fragas, Angelika Griep, Stephanie Schwartz, Róisín M. McManus, Michael T. Heneka

J Neurochem 2023 Feb 17

How location and cellular signaling combine to activate the NLRP3 inflammasome

Akbal A, Dernst A, Lovotti M, Mangan MSJ, McManus RM, Latz E.

Cell Mol Immunol. 2022 Nov;19(11):1201-1214

NLRP3 inflammasome activation drives Tau pathology

Ising C, C Venegas, S Zhang, H Scheiblich, SV Schmidt, A Vieira-Saeker, S Schwartz, S Albasset, RM McManus, D Tejera, A Griep, F Santarelli, F Brosseron, S Opitz, J Stunden, M Merten, R Kayed, DT Golenbock, D Blum, E Latz, L Buée, MT Heneka.