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Mol Neurobiol. 2016 Mar;53(2):1220-1228. doi: 10.1007/s12035-014-9088-8. Epub 2015 Jan 20.

Methylene Blue Improves Brain Mitochondrial ABAD Functions and Decreases Aβ in a Neuroinflammatory Alzheimer's Disease Mouse Model.

Author information

1
Department of Pharmacology & Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
2
Department of Pharmacology & Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt. reham.abdelkader@guc.edu.eg.

Abstract

Methylene blue (MB) phase II clinical trials reported improvements in cognitive functions of Alzheimer's disease (AD) patients. Regarding MB mechanism of action, its antioxidant and mitochondrial protective effects have been previously described. In relation to AD, it has been recently reported that MB reduced amyloid beta (Aβ) levels in AD models. The mitochondrial enzyme amyloid-binding alcohol dehydrogenase (ABAD) has been shown to bind Aβ inducing mitochondrial dysfunction, providing a direct relation between Aβ toxicity and mitochondrial dysfunction occurring in AD. Since it has been reported that inhibiting ABAD protects mitochondrial functions and prevents Aβ-induced toxicity, the aim of the current study was to investigate if the protective effects of MB could be associated with an effect on ABAD levels and functions. The current study shows that MB is able to enhance cell viability, reduce both reactive oxygen species levels and importantly Aβ oligomers in a lipopolysaccharide (LPS) mouse model. Interestingly, ABAD levels were increased in the brains of the LPS mouse model and MB treatment was able to reduce its levels. Given that regulation of the estradiol level is a well-established function of ABAD, brain estradiol level was compared in LPS mouse model and in MB-treated mice. The results of the current study show that MB treatment is able to improve significantly the LPS-induced decrease of estradiol levels in mice brains, indicating its ability to modulate both levels and function of ABAD. These results give a new insight to possible mechanisms of MB in AD.

KEYWORDS:

Alzheimer’s disease; Amyloid beta; Amyloid beta-binding alcohol dehydrogenase; Methylene blue; Mitochondria

PMID:
25601181
DOI:
10.1007/s12035-014-9088-8
[Indexed for MEDLINE]

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