Microglia activated with the toll-like receptor 9 ligand CpG attenuate oligomeric amyloid {beta} neurotoxicity in in vitro and in vivo models of Alzheimer's disease.

ABSTRACT: Soluble oligomeric amyloid beta (oAbeta) 1-42 causes synaptic dysfunction and neuronal injury in Alzheimer's disease (AD). Although accumulation of microglia around senile plaques is a hallmark of AD pathology, the role of microglia in oAbeta1-42 neurotoxicity is not fully understood. Here, we showed that oAbeta but not fibrillar Abeta was neurotoxic, and microglia activated with unmethylated DNA CpG motif (CpG), a ligand for Toll-like receptor 9, attenuated oAbeta1-42 neurotoxicity in primary neuron-microglia co-cultures. CpG enhanced microglial clearance of oAbeta1-42 and induced higher levels of the antioxidant enzyme heme oxygenase-1 in microglia without producing neurotoxic molecules such as nitric oxide and glutamate. Among subclasses of CpGs, class B and class C activated microglia

SUBMITTER: Doi Y 

PROVIDER: S-EPMC2774075 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature