A Novel TREM2-Mediated Link between Diabetes and Cognitive Impairment: Recent Findings and Future Perspectives

Tanaka, Masashi; Inoue, Takayuki; Masuda, Shinji; Ohue‐Kitano, Ryuji; Kusakabe, Toru; Satoh‐Asahara, Noriko

doi:10.4172/2161-0460.1000380

Cited by 3 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although it is increasingly evident that TREM2-expressing microglia play detrimental roles in neurodegenerative diseases (13,17), the pathological implications of TREM2 in CAA remain to be elucidated. In the present study, elevated TREM2 expression levels were significantly associated with the increase in inflammatory markers.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have highlighted the emerging pathological roles of TREM2 and TREM2-expressing microglia in in vivo disease settings (13,17), although the pathophysiological significance of TREM2 and TREM2-expressing microglia in CAA remains unknown in the clinical setting. To investigate the characteristics of TREM2-expressing microglia and the in vivo effects of taxifolin on these cells, we examined associations between expression levels of TREM2 and those of Iba-1, ADAM10, and cytotoxic mediators ( Fig.…”

Section: Taxifolin Exerted No Remarkable Effect On Levels Of Endoplasmicmentioning

confidence: 99%

“…Significant associations have been reported between TREM2 variants and an increased risk for neurodegenerative diseases, including AD (12,13). TREM2 has been demonstrated to have antiinflammatory effects, mainly based on in vitro analyses; however, there is accumulating evidence suggesting that TREM2 and TREM2-expressing microglia may be implicated in the pathology of neuroinflammation and concomitant neurodegeneration in disease settings, characterized by in vivo mouse models such as those for AD, tauopathy, and diet-induced obesity (13,(15)(16)(17)(18). In addition, it was recently reported that sTREM2 was implicated in chronic inflammation through promotion of the survival or activation of macrophages and microglia (19,20).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Inoue

Saitô

Tanaka

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Cerebral amyloid angiopathy (CAA) results from amyloid-β deposition in the cerebrovasculature. It is frequently accompanied by Alzheimer's disease and causes dementia. We recently demonstrated that in a mouse model of CAA, taxifolin improved cerebral blood flow, promoted amyloid-β removal from the brain, and prevented cognitive dysfunction when administered orally. Here we showed that taxifolin inhibited the intracerebral production of amyloid-β through suppressing the ApoE-ERK1/2-amyloid-β precursor protein axis, despite the low permeability of the bloodbrain barrier to taxifolin. Higher expression levels of triggering receptor expressed on myeloid cell 2 (TREM2) were associated with the exacerbation of inflammation in the brain. Taxifolin suppressed inflammation, alleviating the accumulation of TREM2expressing cells in the brain. It also mitigated glutamate levels and oxidative tissue damage and reduced brain levels of active caspases, indicative of apoptotic cell death. Thus, the oral administration of taxifolin had intracerebral pleiotropic neuroprotective effects on CAA through suppressing amyloid-β production and beneficially modulating proinflammatory microglial phenotypes.cerebral amyloid angiopathy | neuroprotection | taxifolin | triggering receptor expressed on myeloid cell 2

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Taxifolin Exerted No Remarkable Effect On Levels Of Endoplasmicmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Inoue

Saitô

Tanaka

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Microglia are the primary cell type responsible for maintaining brain homeostasis and also modulate the neuroinflammatory state [1,2]. A phenotypic shift in microglia from homeostasis to a disease phenotype induces neuroinflammation, which is closely implicated in the pathogenesis of various neurological disorders such as Alzheimer’s disease [2,3].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Suppresses Inflammatory Responses Induced by Lipopolysaccharide through Inhibition of the eIF-2α–ATF4 Pathway in Mouse Microglia

Inoue

Yamakage

Tanaka

et al. 2019

Cells

Self Cite

View full text Add to dashboard Cite

Microglia maintain brain homeostasis and modulate neuroinflammation and are implicated in the pathogenesis of various neurological diseases such as Alzheimer’s disease. In this study, we found that in lipopolysaccharide (LPS)-stimulated microglia, the endoplasmic reticulum (ER) stress-related eIF-2α–ATF4 pathway plays significant roles in TNF-α and IL-6 production, as well as in the inflammasome-mediated production of IL-1β. Furthermore, our analysis revealed that oxytocin (OT), a nonapeptide synthesized in the hypothalamus, suppressed the production of these proinflammatory cytokines by inhibiting activation of the eIF-2α–ATF4 pathway. Our findings therefore suggest a novel anti-inflammatory axis of OT in activated microglia, which would be helpful for developing the novel effective strategies for regulating microglia-associated neuroinflammation.

show abstract