Aβ42 oligomers selectively disrupt neuronal calcium release

摘要: Accumulation of amyloid-β (Aβ) peptides correlates with aging and progression Alzheimer's disease (AD). Aβ peptides, which cause early synaptic dysfunctions, spine loss, memory deficits, also disturb intracellular Ca(2+) homeostasis. By cytosolic endoplasmic reticulum measurements, we here define the short-term effects synthetic Aβ42 on neuronal dynamics. When applied acutely at submicromolar concentration, as either oligomers or monomers, did not release influx. Similarly, 1-hour treatment modified neither resting level nor long-lasting influx caused by KCl-induced depolarization. In contrast, oligomers, but significantly altered from stores opposite inositol 1,4,5-trisphosphate (IP3)- caffeine-induced mobilization without alteration total store content. dysregulation involves metabotropic glutamate receptor 5 requires network activity intact exo-endocytotic machinery, being prevented tetrodotoxin tetanus toxin. These findings support idea that dysfunction is directly involved in neurotoxicity represents a potential therapeutic target AD-like dementia.