Arundic Acid Ameliorates Cerebral Amyloidosis and Gliosis in Alzheimer Transgenic Mice

Mori, Takashi; Town, Terrence; Tan, Jun; Yada, Nobumichi; Horikoshi, Y.; Yamamoto, Junki; Shimoda, Taiji; Kamanaka, Yoshihisa; Tateishi, Narito; Asano, Takao

doi:10.1124/jpet.106.105171

Cited by 63 publications

(68 citation statements)

References 33 publications

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“…Tissue Preparation-Tissue was processed according to our previously described methods (16,18,42,43). At 12 months of age, animals were anesthetized with sodium pentobarbital (50 mg/kg) and euthanized by transcardial perfusion with ice-cold physiological saline containing heparin (10 units/ml).…”

Section: Methodsmentioning

confidence: 99%

“…Image Analysis-Quantitative image analysis was done based on previously validated methods (16,18,42,43). Images were acquired as digitized tagged-image format files to retain maximum resolution using a BX60 microscope with an attached CCD camera system (DP-70, Olympus, Tokyo, Japan), and digital images were routed into a Windows PC for quantitative analyses using SimplePCI software (Hamamatsu Photonics, Hamamatsu, Shizuoka, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, neuroinflammation, as earmarked by ␤-amyloid plaque-associated reactive gliosis and increased expression of proinflammatory cytokines, has been demonstrated in aged transgenic mouse models of cerebral amyloid deposition (18,42,43,(55)(56)(57). To test whether TA impacted neuroinflammatory processes in PSAPP mice, we examined ␤-amyloid plaque-associated microgliosis (by Iba1 antibody) and astrocytosis (using GFAP antibody) immunoreactivity (conventional microgliosis and astrocytosis burden analyses) and quantified brain expression of the proinflammatory cytokines TNF-␣ and IL-1␤.…”

Section: Oral Tannic Acid Treatment Mitigates Hyperactivity Andmentioning

confidence: 99%

“…To assess whether reduced ␤-amyloid burden was specific to a particular plaque size subset or occurred more generally, we performed morphometric analysis of ␤-amyloid plaques in PSAPP-V and PSAPP-TA mice. According to previously described methods (18,16,42,43), plaques were assigned to one of three mutually exclusive categories according to maximum diameter: small (Ͻ 25 m), medium (between 25 and 50 m), or large (Ͼ50 m). Data showed that all three subsets of plaques were significantly reduced in PSAPP-TA versus PSAPP-V mice across all three brain regions examined (Fig.…”

Section: Oral Tannic Acid Treatment Mitigates Hyperactivity Andmentioning

confidence: 99%

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Tannic Acid Is a Natural β-Secretase Inhibitor That Prevents Cognitive Impairment and Mitigates Alzheimer-like Pathology in Transgenic Mice

Mori

Rezai‐Zadeh

Naoki

et al. 2012

Journal of Biological Chemistry

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166

105

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Background: Recent focus has been given to anti-amyloidogenic naturally occurring polyphenols known as flavonoids. Results:The polyphenol tannic acid prevented behavioral impairment and mitigated Alzheimer disease-like pathology. Conclusion: Tannic acid may be prophylactic for Alzheimer disease by inhibiting ␤-secretase activity and mitigating brain pathology. Significance: This nutraceutical approach offers a new class of drug for inhibiting ␤-secretase with few if any side effects.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Oral Tannic Acid Treatment Mitigates Hyperactivity Andmentioning

confidence: 99%

Section: Oral Tannic Acid Treatment Mitigates Hyperactivity Andmentioning

confidence: 99%

See 2 more Smart Citations

Tannic Acid Is a Natural β-Secretase Inhibitor That Prevents Cognitive Impairment and Mitigates Alzheimer-like Pathology in Transgenic Mice

Mori

Rezai‐Zadeh

Naoki

et al. 2012

Journal of Biological Chemistry

Self Cite

166

105

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“…According to previously described methods (22,23,26,36,37), ␤-amyloid deposits were assigned to one of three mutually exclusive categories according to maximum diameter as follows: small (Ͻ 25 m), medium (between 25 and 50 m), or large (Ͼ 50 m). Mean numbers of deposits in all three subsets showed statistically significant decreases in PSAPP-MB versus PSAPP-V mice across all three brain regions examined, with the greatest reduction in the large sized subset, especially in the EC (Figs.…”

Section: Methylene Blue Treatment Reverses Behavioral Benefits Inmentioning

confidence: 99%

Methylene Blue Modulates β-Secretase, Reverses Cerebral Amyloidosis, and Improves Cognition in Transgenic Mice

Mori¹,

Naoki

Segawa

et al. 2014

Journal of Biological Chemistry

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Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in the brains of patients with Alzheimer disease (AD). Here, we tested whether the experimental agent methylene blue (MB), used for treatment of methemoglobinemia, might improve AD-like pathology and behavioral deficits. We orally administered MB to the aged transgenic PSAPP mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid pathology. Beginning at 15 months of age, animals were gavaged with MB (3 mg/kg) or vehicle once daily for 3 months. MB treatment significantly prevented transgene-associated behavioral impairment, including hyperactivity, decreased object recognition, and defective spatial working and reference memory, but it did not alter nontransgenic mouse behavior. Moreover, brain parenchymal and cerebral vascular β-amyloid deposits as well as levels of various Aβ species, including oligomers, were mitigated in MB-treated PSAPP mice. These effects occurred with inhibition of amyloidogenic APP proteolysis. Specifically, β-carboxyl-terminal APP fragment and β-site APP cleaving enzyme 1 protein expression and activity were attenuated. Additionally, treatment of Chinese hamster ovary cells overexpressing human wild-type APP with MB significantly decreased Aβ production and amyloidogenic APP proteolysis. These results underscore the potential for oral MB treatment against AD-related cerebral amyloidosis by modulating the amyloidogenic pathway.

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Current and Future Therapies for Alzheimer Disease

Chakrabarty

Das

Golde

2010

Protein Misfolding Diseases

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Arundic Acid Ameliorates Cerebral Amyloidosis and Gliosis in Alzheimer Transgenic Mice

Cited by 63 publications

References 33 publications

Tannic Acid Is a Natural β-Secretase Inhibitor That Prevents Cognitive Impairment and Mitigates Alzheimer-like Pathology in Transgenic Mice

Tannic Acid Is a Natural β-Secretase Inhibitor That Prevents Cognitive Impairment and Mitigates Alzheimer-like Pathology in Transgenic Mice

Methylene Blue Modulates β-Secretase, Reverses Cerebral Amyloidosis, and Improves Cognition in Transgenic Mice

Current and Future Therapies for Alzheimer Disease

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