Dietary regulation of PI3K/AKT/GSK-3β pathway in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is characterized by the formation of senile plaques and neurofibrillary tangles composed of phosphorylated Tau. Several findings suggest that correcting signal dysregulation for Tau phosphorylation in AD may offer a potential therapeutic approach. The PI3K/AKT/GSK-3β pathway has been shown to play a pivotal role in neuroprotection, enhancing cell survival by stimulating cell proliferation and inhibiting apoptosis. This pathway appears to be crucial in AD because it promotes protein hyper-phosphorylation in Tau. Understanding those regulations may provide a better efficacy of new therapeutic approaches. In this review, we summarize advances in the involvement of the PI3K/AKT/GSK-3β pathways in cell signaling of neuronal cells. We also review recent studies on the features of several diets and the signaling pathway involved in AD.

The Role of 6-Gingerol on Inhibiting Amyloid β Protein-Induced Apoptosis in PC12 Cells

“…39 Hyper-phosphorylated Tau is the major component of the paired helical filaments that accumulate in degenerating neurons in AD and other neurodegenerative diseases. 40 Thus, the AKT/GSK-3b pathway seems to be vital for AD because it regulates Tau hyper-phosphorylation in cells. Our study indicated that 6-gingerol could activate the AKT/GSK-3b pathway through activation of AKT and inhibition of GSK-3b, indicating that 6-gingerol exerted neuroprotective effects through the AKT/GSK-3b pathway.…”

“…After 5 days of induced differentiation by NGF, the cells were treated with prepared Ab 1-42 (5, 10, and 20 lM) for 24, 48, and 72 hr, and cell viability was then evaluated with an MTT assay. To determine the protective effects of 6-gingerol on Ab 1-42 -induced cell injury, PC12 cells were treated with 6-gingerol at different concentrations (40,80,120,200, and 300 lM) for 4 hr, and the cells were then incubated with 10 lM Ab 1-42 for another 48 hr. Then, the cells were incubated in fresh F12K medium containing 0.5 mg/mL MTT at 37°C for 4 hr.…”

Role of Presenilin-1 in Modulating Glycogen Synthase Kinase 3 β Expression in the Pathogenesis of Alzheimer’s Disease

“…It is also involved in regulation of many transcription factors, including brain-derived neurotrophic factor (BDNF), activator protein-1, cyclic AMP response element binding protein, heat shock factor-1, nuclear factor of activated T cells, Myc, CCAAT/enhancer binding protein, NF-kβ, tau (where it is the most documented kinase involved in tau hyperphosphorylation) and β -catenin (14,47). Levels of GSK3β are enhanced in AD as compared to nondiseased human brains, thereby providing concomitant evidence regarding neuronal demise due to the action of 401 ) are conserved in all species examined.…”

“…As activated Akt phosphorylates target proteins involved in cell survival, cell cycling, angiogenesis, and in metabolism for neuroprotection, Akt activation may play a therapeutic role in neurodegenerative diseases. Akt is thus an important regulator of cell survival and apoptosis (47).…”

“…One of the presenilin -1 (PS-1) interacting proteins is GSK3β which is ubiquitously expressed in the brain and localizes predominantly in the neurons where it is involved in regulation of cell survival, neuronal and synaptic plasticity, memory formation, assimilation and gene expression (14,46,47). It is also involved in regulation of many transcription factors, including brain-derived neurotrophic factor (BDNF), activator protein-1, cyclic AMP response element binding protein, heat shock factor-1, nuclear factor of activated T cells, Myc, CCAAT/enhancer binding protein, NF-kβ, tau (where it is the most documented kinase involved in tau hyperphosphorylation) and β -catenin (14,47).…”