Publisher Correction: Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease

Mesquita, Sandro Dá; Louveau, Antoine; Vaccari, Andrea; Smirnov, Igor; Cornelison, R. Chase; Kingsmore, Kathryn M.; Contarino, Christian; Önengüt-Gümüşcü, Suna; Farber, Emily; Raper, Daniel; Viar, Kenneth E.; Powell, Romie D.; Baker, Wendy; Dabhi, Nisha; Bai, Robin; Cao, Rui; Hu, Song; Rich, Stephen S.; Munson, Jennifer M.; Lopes, M. Beatriz S.; Overall, Christopher C.; Acton, Scott T.; Kipnis, Jonathan

doi:10.1038/s41586-018-0689-7

“…Neuroinflammation is a key factor in the neurodegenerative process of AD [11]. This process involves an initial inflammatory stimulus (Aβ, pro-inflammatory cytokines, chemokines and the generation of reactive oxygen species) that triggers microglia, the resident macrophage within the central nervous system (CNS) [12][13][14][15]. In addition, monocytes recruited from the periphery can interact with microglia to influence the expression of amyloid-beta [16,17].…”

Section: Introductionmentioning

confidence: 99%

Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer’s disease progression based on the “brain-gut” axis through multiple integrated omics

Gu

¹

,

Zhou

²

,

Zhou

³

et al. 2021

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Background In recent years, excellent results have suggested an association between the “brain-gut” axis and Alzheimer’s disease (AD) progression, yet the role of the “brain-gut” axis in AD pathogenesis still remains obscure. Herein, we provided a potential link between the central and peripheral neuroinflammatory disorders in AD progression. Methods The Morris water maze (MWM) test, immunohistochemistry, ELISA, ProcartaPlex Multiplex immunoassay, multiple LC-MS/MS methods, and the V3-V4 regions of 16S rRNA genes were applied to explore potential biomarkers. Results In Tg-APP/PS1 mice, gut dysbiosis and lipid metabolism were highly associated with AD-like neuroinflammation. The combination of inflammatory factors (IL-6 and INF-γ), phosphatidylcholines (PCs) and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD. Huanglian Jiedu decoction (HLJDD) suppressed gut dysbiosis and the associated Aβ accumulation, harnessed neuroinflammation and reversed cognitive impairment. Conclusion Together, our findings highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorder in AD progression. This integrated metabolomics approach showed its potential to understand the complex mechanisms of HLJDD in the treatment of AD.

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“…In the case of ASPD, we have already shown that ASPD are selectively formed in excitatory neurons and secreted (Komura et al, 2019). Therefore, it is natural to consider that ASPD are delivered to the cerebral blood vessels through apolipoprotein E (ApoE), clusterin, or brain meningeal lymphatics, as reported previously (Beeg et al, 2016, da Mesquita et al, 2018Garai et al, 2014;Nelson et al, 2017). However, other possibilities, e.g., formation of ASPD in the cerebral blood microvessels, cannot be excluded, because Ab precursor protein (APP) is also expressed on the surface of cerebral endothelial cells, even though the APP isoform profiles in endothelial cells are different from those in neurons (Grinberg et al, 2012;Kakuda et al, 2017;Kitazume et al, 2010).…”

Section: Article Discussionmentioning

confidence: 82%

Alzheimer's Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway in brain vascular endothelial cells

Sasahara

¹

,

Satomura

²

,

Tada

³

et al. 2021

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show abstract

“…In the case of ASPD, we have already shown that ASPD are selectively formed in excitatory neurons and secreted (Komura et al, 2019). Therefore, it is natural to consider that ASPD are delivered to the cerebral blood vessels through apolipoprotein E (ApoE), clusterin, or brain meningeal lymphatics, as reported previously (Beeg et al, 2016;Da Mesquita et al, 2018;Garai, Verghese, Baban, Holtzman, & Frieden, 2014;Nelson, Sagare, & Zlokovic, 2017). However, other possibilities, e.g.…”

Section: Discussionmentioning

confidence: 97%

Alzheimer’s Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway

Sasahara

¹

,

Satomura

²

,

Tada

³

et al. 2020

Preprint

1

0

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Amyloid β-protein (Aβ) may contribute to worsening of Alzheimer’s disease (AD) through vascular dysfunction, but the actual molecular mechanisms remain controversial. Using ex-vivo blood vessels and primary endothelial cells derived from human brain microvessels, we revealed that patient-derived Aβ assemblies, termed amylospheroids (ASPD), exist on the microvascular surface in patient brains and inhibit vasorelaxation through binding to the α3 subunit of sodium, potassium-ATPase (NAKα3) on endothelial cells. Interestingly, NAKα3 also serves as the toxic target of ASPD in neurons. ASPD elicit neurodegeneration through calcium overload, while ASPD suppress vasorelaxation by inhibiting nitric oxide (NO) production. ASPD-NAKα3 interaction on cerebrovascular endothelial cells disturbs the NO release by inactivating endothelial NO synthase through mitochondrial reactive oxygen species and protein kinase C. The findings suggest that ASPD may dually contribute to neuronal and vascular pathologies through binding to NAKα3. Thus, blocking the ASPD-NAKα3 interaction may be a useful target for AD therapy.

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Publisher Correction: Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease

Cited by 13 publications

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Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer’s disease progression based on the “brain-gut” axis through multiple integrated omics

Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer’s disease progression based on the “brain-gut” axis through multiple integrated omics

Alzheimer's Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway in brain vascular endothelial cells

Alzheimer’s Aβ assembly binds sodium pump and blocks endothelial NOS activity via ROS-PKC pathway

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