Curcumin Attenuates Beta-Amyloid-Induced Neuroinflammation via Activation of Peroxisome Proliferator-Activated Receptor-Gamma Function in a Rat Model of Alzheimer's Disease

Abstract

Neuroinflammation is known to have a pivotal role in the pathogenesis of Alzheimer's disease (AD), and curcumin has been reported to have therapeutical effects on AD because of its anti-inflammatory effects. Curcumin is not only a potent PPARγ agonist, but also has neuroprotective effects on cerebral ischemic injury. However, whether PPARγ activated by curcumin is responsible for the anti-neuroinflammation and neuroprotection on AD remains unclear, and needs to be further investigated. Here, using both APP/PS1 transgenic mice and beta-amyloid-induced neuroinflammation in mixed neuronal/glial cultures, we showed that curcumin significantly alleviated spatial memory deficits in APP/PS1 mice and promoted cholinergic neuronal function in vivo and in vitro. Curcumin also reduced the activation of microglia and astrocytes, as well as cytokine production and inhibited nuclear factor kappa B (NF-κB) signaling pathway, suggesting the beneficial effects of curcumin on AD are attributable to the suppression of neuroinflammation. Attenuation of these beneficial effects occurred when co-administrated with PPARγ antagonist GW9662 or silence of PPARγ gene expression, indicating that PPARγ might be involved in anti-inflammatory effects. Circular dichroism and co-immunoprecipitation analysis showed that curcumin directly bound to PPARγ and increased the transcriptional activity and protein levels of PPARγ. Taking together, these data suggested that PPARγ might be a potential target of curcumin, acting to alleviate neuroinflammation and improve neuronal function in AD.

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

“…Liu and colleagues (2016) [95] studied the curcumin’s effects against neuroinflammation in both APP/PS1 transgenic mice and beta-amyloid-induced neuroinflammation in mixed neuronal/glial cultures. They showed that curcumin significantly alleviated spatial memory deficits in APP/PS1 mice and promoted cholinergic neuronal function in vivo and in vitro .…”

“…Circular dichroism and co-immunoprecipitation analysis showed that curcumin directly bound to PPARγ and increased the transcriptional activity and protein levels of PPARγ. Taking together, these data suggested that PPARγ might be a potential target of curcumin, acting to alleviate neuroinflammation and improve neuronal function in AD [95]. …”

Benefits of curcumin in brain disorders

“…Peroxisome proliferator‐activated receptor gamma (PPAR‐γ) is a ligand‐activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. PPAR‐γ influences the activity of several intracellular second messengers and their signaling cascade, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fate . Recent studies have reported that activation of PPAR‐γ reduces the development and progression of neurodegenerative diseases by altering the expression of NF‐κB cascade .…”

“…PPAR-γ influences the activity of several intracellular second messengers and their signaling cascade, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fate. [130][131][132] Recent studies have reported that activation of PPAR-γ reduces the development and progression of neurodegenerative diseases by altering the expression of NF-κB cascade. 131,133,134 PPAR-γ is highly expressed in hippocampal region of the brain.…”

“…[130][131][132] Recent studies have reported that activation of PPAR-γ reduces the development and progression of neurodegenerative diseases by altering the expression of NF-κB cascade. 131,133,134 PPAR-γ is highly expressed in hippocampal region of the brain. 135 PPAR-γ directly or indirectly influences the expression of genes (TFAM, NRF1, NRF2, Bax, and Bcl-2) that are involved in neurodegeneration.…”