Abstract:
:The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effects of this drug. Here, we demonstrate that dimebon enhances the resistance of the isolated rat brain and liver mitochondria to the induction of mitochondrial permeability transition (MPT) by calcium ions even in the presence of atractyloside, a MPT pore (MPTP) opener, but is ineffective against atractyloside-induced mitochondria swelling. Unlike cyclosporine A (CsA), a MPTP inhibitor, Dimebon does not influence the adenine nucleotide translocase (ANT) conformational changes and is not able to prevent the MPT of de-energized mitochondria. Using three different assays, and using amyloid-β peptide for inducing mitochondrial toxicity, we show that the influence of dimebon on the calcium retention capacity (CRC) of mitochondria depends on the mode of calcium addition. No obvious influence of dimebon on CRC was observed under the conditions of calcium infusion in the pump mode but the increase of CRC of rat brain mitochondria was observed when calcium was added in the bolus mode; the addition of calcium in the single pulse mode led to the increase of the lag period of calcium efflux from mitochondria. From these studies it is shown that dimebon is effective against amyloid-β (Aβ) potentiated mitochondrial swelling and decrease of calcium retention capacity (CRC) of the brain mitochondria.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Shevtsova EF,Vinogradova DV,Kireeva EG,Reddy VP,Aliev G,Bachurin SOdoi
10.2174/1567205011666140505094808subject
Has Abstractpub_date
2014-01-01 00:00:00pages
422-9issue
5eissn
1567-2050issn
1875-5828pii
CAR-EPUB-60344journal_volume
11pub_type
杂志文章abstract::The field of aging and dementia research is advancing rapidly toward the stage of earlier identification of clinical symptoms. Ultimately, clinicians would like to be able to identify individuals who are asymptomatic but at risk for developing dementia. In the interim, the construct of mild cognitive impairment (MCI) ...
journal_title:Current Alzheimer research
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pub_type: 杂志文章,随机对照试验
doi:10.2174/156720509787313961
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pub_type: 杂志文章,收录出版
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