Identification of thyrotropin-releasing hormone as hippocampal glutaminyl cyclase substrate in neurons and reactive astrocytes.

摘要: Recently, Aβ peptide variants with an N-terminal truncation and pyroglutamate modification were identified shown to be highly neurotoxic prone aggregation. This of is catalyzed by glutaminyl cyclase (QC) pharmacological inhibition QC diminishes deposition accompanying gliosis ameliorates memory impairment in transgenic mouse models Alzheimer's disease (AD). expression was initially described the hypothalamus, where thyrotropin-releasing hormone (TRH) one its physiological substrates. In addition hormonal role, a novel neuroprotective function TRH following excitotoxicity Aβ-mediated neurotoxicity has been reported hippocampus. Functionally matching this finding, we recently demonstrated hippocampal interneurons brain. Here, detected neuronal co-expression hippocampus young adult wild type mice using double immunofluorescence labeling. provides evidence for being substrate Additionally, neocortex aged but not amyloid precursor protein increase mRNA levels found compared littermates. phenomenon observed hippocampus, which later affected pathology. However, - correlation between revealed. co-regulation enzyme reflected co-induction both proteins reactive astrocytes proximity deposits. Also, primary upon stimulation.