Kainate Receptor Activation Enhances Amyloidogenic Processing of APP in Astrocytes.

摘要: Kainic acid (KA) is an analogue of the excitatory neurotransmitter glutamate that, when injected systemically into adult rats, can trigger seizures and progressive neuronal loss in a manner that mirrors neuropathology human mesial temporal lobe epilepsy. However, biomolecular mechanisms responsible for occurs as consequence this treatment remains elusive. We have recently reported toxicity induced by KA partly be mediated astrocyte-derived amyloid β (Aβ) peptides, which are critical development Alzheimer's disease (AD). Nonetheless, little known how influence precursor protein (APP) levels processing astrocytes. Thus, present study using U-373 astrocytoma rat primary astrocytes, we evaluated role on APP metabolism. Our results revealed increased its cleaved products (α-/β-CTFs) cultured without altering cell viability. The cellular secretory Aβ1-40/Aβ1-42 were markedly KA-treated also demonstrated steady-state APP-secretases not altered but activity γ-secretase enhanced astrocytoma. Furthermore, selective receptor antagonists, showed effects activation kainate receptors NMDA or AMPA receptors. These suggest enhance amyloidogenic activating own leading to production/secretion Aβ-related peptides from activated astrocytes may contribute pathogenesis