BACKGROUND: @entity195 ( @entity195 ) is characterized by senile plaques, extracellular deposits composed primarily of @entity5357 ( @entity5357 ), and @entity3072 , which are abnormal intracellular inclusions containing hyperphosphorylated tau. The amyloid cascade hypothesis posits that the deposition of @entity5357 in the brain parenchyma initiates a sequence of events that leads to @entity303 . However, the molecular process by which the extracellular accumulation of @entity5357 peptides promotes intracellular pathologic changes in tau filaments remains unclear. To elucidate this process, we presumed that astrocytes might trigger neuronal reactions, leading to tau phosphorylation. In this study, we examined @entity195 pathology from the perspective of the astrocyte-neuron interaction. RESULTS: A cytokine-array analysis revealed that @entity5357 stimulates astrocytes to release several chemical mediators that are primarily related to @entity32 and cell adhesion. Among those mediators, @entity2301 ( @entity2301 ) was highly upregulated. In @entity195 brains, the expression of @entity2301 was found to be increased by western blot analysis, and increased expression of @entity2301 was observed in astrocytes via fluorescence microscopy. In addition, we reproduced the increase in @entity2301 after treatment with @entity5357 using @entity1 @entity816 cell lines and found that @entity2301 was expressed via calcineurin. In @entity195 brains, the activated forms of calcineurin were found to be increased by western blot analysis, and increased expression of calcineurin was observed in astrocytes via fluorescence microscopy. When Ser9 of glycogen synthase kinase-3b ( @entity9459 ) is phosphorylated, @entity9459 is controlled and tau phosphorylation is suppressed. @entity5357 suppresses the phosphorylation of @entity9459 , leading to tau phosphorylation. In this study, we found that IGF-   suppressed tau phosphorylation induced by @entity5357 , although @entity2301 inhibited this property of IGF-  . As a result, @entity2301 contributed to tau phosphorylation and cell death induced by @entity5357 . CONCLUSIONS: Our study suggested that calcineurin in astrocytes was activated by @entity5357 , leading to @entity2301 release. We further demonstrated that @entity2301 produced by astrocytes induced tau phosphorylation in neurons. Our study provides novel insights into the role of astrocytes in the induction of tau phosphorylation and suggests that @entity2301 could be an important link between @entity5357 and tau pathology and an important therapeutic target.

The participation of XXXX released by astrocytes in the pathology of @entity195 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity2301 :: ('3486', 'Gene') :: ['IGFBP-3', 'insulin-like growth factor (IGF)-binding protein 3'] @entity303 :: ('MESH:D003704', 'Disease') :: ['dementia'] @entity3072 :: ('MESH:C536599', 'Disease') :: ['neurofibrillary tangles'] @entity5357 :: ('MESH:D012497', 'Disease') :: ['amyloid-beta', 'Ab'] @entity816 :: ('MESH:D001254', 'Disease') :: ['astrocytoma'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity9459 :: ('2932', 'Gene') :: ['GSK-3b']
@entity2301 :: (3486,Gene) :: ['insulin-like growth factor-binding protein 3']
