|| Checking for direct PDF access through Ovid
Alzheimer’s disease (AD), the most common chronic neurodegenerative disease, is pathologically characterized by the formation of neurofibrillary tangles because of hyperphosphorylation of tau protein and extracellular deposits of amyloid-β (Aβ) protein termed senile plaques. Recent studies indicate that neuronal apoptosis caused by chronic neuroinflammation is one of the important pathogenesis of AD. Transforming growth factor (TGF)-β1 is a pleiotropic cytokine with immunosuppressive and anti-inflammatory properties. However, it is poorly known whether the anti-inflammatory property of TGF-β1 is involved in a neuroprotection in AD. Here, an AD cell model of hippocampal neurons induced by Aβ1–42 was used to show an anti-inflammatory and neuroprotective effect of TGF-β1 through its receptor transforming growth factor-β receptor type I (TβR-I). As expected, Aβ1–42-induced an upregulation in neuronal expression of amyloid precursor protein (APP), tumor necrosis factor-α, cyclooxygenase-2, Bax, cleaved caspase-3, and cleaved caspase-9, and a downregulation in the expression of Bcl-2, as well as an increase in the number of NeuN/terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) double-positive cells. TGF-β1 pretreatment reduced the Aβ1–42-induced effects of upregulating APP, tumor necrosis factor-α, Bax, cleaved caspase-3 and cleaved caspase-9, and downregulating Bcl-2, in addition to increasing NeuN+TUNEL+ cell number. TβR-I expression in hippocampal neurons was downregulated by Aβ1–42 exposure, but upregulated by TGF-β1 pretreatment. Silencing of the TβR-I gene in the neurons abolished the anti-inflammatory and antiapoptotic effects of TGF-β1 in the Aβ1–42-induced AD cell model. These findings suggest that TGF-β1 protects neurons against Aβ1–42-induced neuronal inflammation and apoptosis by activation of TβR-I.