Topic: TrkB-ICD

The neuroprotective BDNF/TrkB-FL system is compromised in Alzheimer’s disease (AD). Amyloid-beta triggers calpain-mediated TrkB-FL receptor cleavage, leading to TrkB-ICD formation, a novel intracellular toxic fragment. Biological fluids are used to pinpoint potential disease biomarkers and extracellular vesicles (EVs) are cell-specific carriers of promising pathological biomarkers. Thus, this work aimed to investigate the presence of TrkB-ICD in AD human samples and EVs. Protein and RNA was extracted from human AD post-mortem brain samples classified according to the Braak staging (stages 0-II

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,