Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse Models of Alzheimer's Disease.

Unlabelled: Increasing evidence supports a role of neuroinflammation in the pathogenesis of Alzheimer's disease (AD). Previously, we identified a neuron-glia signaling pathway whereby Aβ acts as an upstream activator of astroglial nuclear factor kappa B (NF-κB), leading to the release of complement C3, which acts on the neuronal C3a receptor (C3aR) to influence dendritic morphology and cognitive function. Here we report that astrocytic complement activation also regulates Aβ dynamics in vitro and amyloid pathology in AD mouse models through microglial C3aR.

Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis.

A critical role of the amyloid precursor protein (APP) in Alzheimer's disease (AD) pathogenesis has been well established. However, the physiological function of APP remains elusive and much debated. We reported previously that the APP family of proteins is essential in mediating the developing neuromuscular synapse.

Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death.

Neuronal cell death after DNA damage requires p53 and Bax, but the mechanism by which p53 activation leads to Bax translocation and cell death in neurons is not known. We report here that Peg3/Pw1 is up-regulated after DNA damage in cortical neurons in a p53-dependent manner. Overexpression of Peg3/Pw1 leads to decreased neuronal viability.