Plasma Carbonic Anhydrase II protein is Elevated in Alzheimer's Disease

Jang, Bong Geom; Yun, Sang Moon; Ahn, Kyungsook; Song, Jun‐Yeob; Jo, Sangmee Ahn; Kim, Young‐Yul; Kim, Doh Kwan; Park, Moon Ho; Han, Changsu; Koh, Young Ho

doi:10.3233/jad-2010-100384

Cited by 40 publications

(35 citation statements)

References 23 publications

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“…15 Synthetic aminoisoflavone derivatives have been demonstrated previously to have inhibitory activity against various isoforms of human carbonic anhydrase (hCAI and hCAII), 19 a metalloenzyme that has been occasionally linked to AD. 20 Thus, we were curious to know whether the family of compounds could target and modulate another aspect of AD-related reactivity. The design of the new aminoisoflavones 1 - 4 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

et al. 2014

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Metal ion homeostasis in conjunction with amyloid-β (Aβ) aggregation in the brain has been implicated in Alzheimer’s disease (AD) pathogenesis. To uncover the interplay between metal ions and Aβ peptides, synthetic, multifunctional small molecules have been employed to modulate Aβ aggregation in vitro. Naturally occurring flavonoids have emerged as a valuable class of compounds for this purpose due to their ability to modulate both metal-free and metal-induced Aβ aggregation. Although, flavonoids have shown anti-amyloidogenic effects, the structural moieties of flavonoids responsible for such reactivity have not been fully identified. In order to understand the structure-interaction-reactivity relationship within the flavonoid family for metal-free and metal-associated Aβ, we designed, synthesized, and characterized a set of isoflavone derivatives, aminoisoflavones (1-4), that displayed reactivity (i.e., modulation of Aβ aggregation) in vitro. NMR studies revealed a potential binding site for aminoisoflavones between the N-terminal loop and central helix on prefibrillar Aβ different from the non-specific binding observed for other flavonoids. The absence or presence of the catechol group differentiated the binding affinities and enthalpy/entropy balance between aminoisoflavones and Aβ. Furthermore, having a catechol group influenced the binding mode with fibrillar Aβ. Inclusion of additional substituents moderately tuned the impact of aminoisoflavones on Aβ aggregation. Overall, through these studies, we obtained valuable insights on the requirements for parity among metal chelation, intermolecular interactions, and substituent variation for Aβ interaction.

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Section: Resultsmentioning

confidence: 99%

Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

et al. 2014

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“…Cognitive functioning and memory impairments of subjects were assessed using a Korean version of (McKhann et al, 1984). MCI was diagnosed on the basis of the Mayo Clinic criteria (Petersen et al, 1999) as described previously (Jang et al, 2010;Kim et al, 2007). The study flow diagram in Fig EV11A provides further details on sample use.…”

Section: Subjectsmentioning

confidence: 99%

Alteration of Vascular Endothelial Cadherin in Alzheimer’s Disease Patient and Mouse Model

Lee

Cho

Lim

et al. 2018

Preprint

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Alzheimer's disease (AD) is characterized by amyloid plaques and pathologic cerebrovascular remodeling. Cerebrovascular abnormalities may contribute to the pathology of AD, but the molecular mechanisms are not fully understood. In this study, we evaluated blood-brain barrier (BBB) disruption and the role of VE-cadherin in the progression of amyloid pathology. Here, we determined that levels of VE-cadherin are decreased in brain vessels of AD patients and mouse model of AD. In vitro experiments showed that the disappearance of VE-cadherin by betaamyloid at the endothelial cell surface was due to cleavage of VE-cadherin. VE-cadherin cleavage was inhibited by a γ-secretase and ADAM10 inhibitor. The disappearance of VE-cadherin in brain vessels was also seen in amyloid precursor protein transgenic mice. In the postmortem brain of individuals with AD, furthermore, levels of VE-cadherin were significantly reduced in vessels. Dementia patients showed a distinct blood biochemical profile characterized by high soluble VE-cadherin (sVEC). There was a strong association between plasma sVEC (adjusted odds ratio = 3.41, P < 0.001) and dementia. These results suggest that measurements of plasma VE-cadherin could have the potential for predicting the risk of progressive AD.

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“…Gels were scanned and analyzed using Quantity One software (Bio-Rad). Meanwhile, the other set was transferred to PVDF membrane [18,19] and analyzed by Western blot as described above. The variation of b-actin expression in plasma from MDD patients and HCs was evaluated by total CV.…”

Section: Effect Of Depression On B-actin Protein Expressionmentioning

confidence: 99%

β-Actin as a loading control for plasma-based Western blot analysis of major depressive disorder patients

Zhang¹,

Yang²,

Zhou³

et al. 2012

Analytical Biochemistry

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Plasma Carbonic Anhydrase II protein is Elevated in Alzheimer's Disease

Cited by 40 publications

References 23 publications

Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β

Alteration of Vascular Endothelial Cadherin in Alzheimer’s Disease Patient and Mouse Model

β-Actin as a loading control for plasma-based Western blot analysis of major depressive disorder patients

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