کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5739076 1615358 2017 19 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Review articleAlternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots
ترجمه فارسی عنوان
بررسی انتقال الکترون الکترونیک میتوکندری خارجی برای درمان بیماری های نورودنراتیو و سرطان: متیلن آبی نقاط اتصال
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


- Reprogramming energetic metabolism is a common feature for neurodegenerative diseases and cancers.
- Methylene blue functions as an alternative mitochondrial electron transfer carrier, enhancing bioenergetics and inhibiting biosynthetics.
- Methylene blue provides protective effect in rodent models of Parkinson disease, Alzheimer's disease, Huntington's disease, and Friedreich's ataxia.
- Methylene blue reverses Warburg's effect and inhibits cancers proliferation.
- Alternative mitochondrial electron transfer may provide a common novel therapeutic mechanism for cancers and neurodegenerative diseases.

Brain has exceptional high requirement for energy metabolism with glucose as the exclusive energy source. Decrease of brain energy metabolism and glucose uptake has been found in patients of Alzheimer's, Parkinson's and other neurodegenerative diseases, providing a clear link between neurodegenerative disorders and energy metabolism. On the other hand, cancers, including glioblastoma, have increased glucose uptake and rely on aerobic glycolysis for energy metabolism. The switch of high efficient oxidative phosphorylation to low efficient aerobic glycolysis pathway (Warburg effect) provides macromolecule for biosynthesis and proliferation. Current research indicates that methylene blue, a century old drug, can receive electron from NADH in the presence of complex I and donates it to cytochrome c, providing an alternative electron transfer pathway. Methylene blue increases oxygen consumption, decrease glycolysis, and increases glucose uptake in vitro. Methylene blue enhances glucose uptake and regional cerebral blood flow in rats upon acute treatment. In addition, methylene blue provides protective effect in neuron and astrocyte against various insults in vitro and in rodent models of Alzheimer's, Parkinson's, and Huntington's disease. In glioblastoma cells, methylene blue reverses Warburg effect by enhancing mitochondrial oxidative phosphorylation, arrests glioma cell cycle at s-phase, and inhibits glioma cell proliferation. Accordingly, methylene blue activates AMP-activated protein kinase, inhibits downstream acetyl-coA carboxylase and cyclin-dependent kinases. In summary, there is accumulating evidence providing a proof of concept that enhancement of mitochondrial oxidative phosphorylation via alternative mitochondrial electron transfer may offer protective action against neurodegenerative diseases and inhibit cancers proliferation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Neurobiology - Volume 157, October 2017, Pages 273-291
نویسندگان
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