Cerebrovascular degradation of TRKB by MMP9 in the diabetic brain.

ABSTRACT: Diabetes elevates the risk for neurological diseases, but little is known about the underlying mechanisms. Brain-derived neurotrophic factor (BDNF) is secreted by microvascular endothelial cells (ECs) in the brain, functioning as a neuroprotectant through the activation of the neurotrophic tyrosine kinase receptor TRKB. In a rat model of streptozotocin-induced hyperglycemia, we found that endothelial activation of MMP9 altered TRKB-dependent trophic pathways by degrading TRKB in neurons. Treatment of brain microvascular ECs with advanced glycation endproducts (AGE), a metabolite commonly elevated in diabetic patients, increased MMP9 activation, similar to in vivo findings. Recombinant human MMP9 degraded the TRKB ectodomain in primary neuronal cultures, suggesting that TRKB could be a subs

SUBMITTER: Navaratna D 

PROVIDER: S-EPMC3726155 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature