Transforming growth factor-beta (TGF-β) type II receptor (TβRII) levels are extremely low in the brain tissue of patients with Alzheimer's disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specifc adapter protein, protects TβRII from degradation and ensures the effective conduction of TGF-β1/SMAD signaling. Prof. Jun Liu and team from Norman Bethune First Hospital of Jilin University in China used an adenoviral vector to overexpress Dab2 in the APP/PS1 transgenic mouse model of Alzheimer's disease, and investigated the regulatory effect of Dab2 protein on transforming growth factor-β1/SMAD signaling and brain injury in Alzheimer's disease. They found that after Dab2 expression, hippocampal TβRII and p-SMAD2/3 levels were significantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor-β and interleulin-6 levels and neuronal loss were signifcantly attenuated in APP/PS1 mouse brain tissue. These findings, published in the Neural Regeneration Research (Vol. 9, No. 1, 2014), suggest that Dab2 can exhibit neuroprotective effects in Alzheimer's disease by regulating TGF-β1/SMAD signaling.
By fuorescence microscopy, Iba1-positive microglia (arrows, green) with irregular morphology and many neurites were observed in the hippocampi of Alzheimer's disease mice after Dab2 overexpression. Scale bars: 10 μm.
(Photo Credit: Neural Regeneration Research)
Source: Neural Regeneration Research