Progress in drug development for Alzheimer's disease: An overview in relation to mitochondrial energy metabolism

Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiologi...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2016-10, Vol.121, p.774-784
Main Authors: Hroudová, Jana, Singh, Namrata, Fišar, Zdeněk, Ghosh, Kallol K.
Format: Article
Language:English
Subjects:
Alzheimer Disease - drug therapy
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid-beta binding alcohol dehydrogenase modulators
Animals
Cholinesterase inhibitors
Drug Discovery - methods
Energy Metabolism - drug effects
Humans
Mitochondria - drug effects
Mitochondria - metabolism
Monoamine oxidase (MAO) inhibitors
Monoamine Oxidase Inhibitors - chemistry
Monoamine Oxidase Inhibitors - metabolism
Monoamine Oxidase Inhibitors - pharmacology
Monoamine Oxidase Inhibitors - therapeutic use
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Summary:Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity. [Display omitted] •Mitochondrial dysfunctions in Alzheimer's disease are elucidated.•Newly synthesized drugs target multiple Alzheimer's disease pathophysiological pathways.•Cholinesterase and monoamine oxidase inhibitors are reviewed in relation to energy metabolism.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2016.03.084