Aβ toxicity in primary cultured neurons.

The aggregation of beta-amyloid (Aβ) into soluble oligomers is considered an early event in Alzheimer's disease. Furthermore, the presence of these aggregates seems to lead to neurodegeneration in the context of this disease. However, the mechanisms underlying Aβ-induced neurotoxicity are not completely understood.

The novel calpain inhibitor A-705253 potently inhibits oligomeric beta-amyloid-induced dynamin 1 and tau cleavage in hippocampal neurons.

We have previously shown that beta-amyloid (Abeta) oligomers induced dynamin 1 and tau cleavage in cultured hippocampal neurons. As a result of this cleavage, dynamin 1 levels decreased and a toxic tau fragment was generated. Abeta-induced cleavage of these proteins was calpain-mediated and impacted both synaptic vesicle recycling and the integrity of neuronal processes [Kelly, B.