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 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.
Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic.
Jana
J
Hroudová
Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic.
Namrata
N
Singh
Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic.
Zdeněk
Z
Fišar
School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur, CG, 492010, India. Electronic address: kallolkghosh@yahoo.com.
Kallol K
KK
Ghosh
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D008996:Monoamine Oxidase Inhibitors
Alzheimer's disease; Amyloid-beta binding alcohol dehydrogenase modulators; Cholinesterase inhibitors; Monoamine oxidase (MAO) inhibitors