A potential new source of TrkB dysregulation: Microglia possess the machinery for BDNF receptor cleavage
Mafalda Ferreira-Manso, Tiago Costa-Coelho, Sara Inteiro-Oliveira, Ana M. Sebastião, Adelaide Fernandes, Maria José Diógenes · FENS Forum 2024
The signalling pathways mediated by BDNF are impaired in Alzheimer’s disease (AD) due to the cleavage of its receptor, TrkB-FL. Amyloid-Beta peptide (Aβ) accumulation promotes the overactivation of NMDA receptors, allowing for a major calcium influx. As a consequence, calcium-dependent calpains proteases become activated, leading to TrkB-FL receptor cleavage and the formation of a new fragment, TrkB-ICD. Data from primary neuronal cultures show that TrkB-ICD is a stable fragment able to phosphorylate nuclear and axonal proteins and promotes transcriptomic and proteomic alterations. Alongside,
ePoster · Neuroscience