| Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death. | |
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MedLine Citation:
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PMID: 20555134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dimebon, a drug currently being evaluated in multiple Phase III Alzheimer's disease trials, has previously been shown to have effects on isolated mitochondria at muM concentrations. Here the effects of nM concentrations of Dimebon on mitochondrial function were investigated both in primary mouse cortical neurons and human neuroblastoma cells (SH-SY5Y). Under non-stress conditions nM concentrations of Dimebon increased succinate dehydrogenase activity (MTT-assay), mitochondrial membrane potential (DeltaPsim), and cellular ATP levels. Dimebon treatment had no effect on mitochondria DNA content, implying that mitochondrial biogenesis was not induced. Under stress conditions, mitochondria in Dimebon-treated neurons showed increased resistance to elevated intracellular calcium concentrations, thus, maintaining their DeltaPsim throughout the experiment, in contrast to control neurons, which rapidly lost their DeltaPsim. Moreover, we show that serum-starved differentiated SH-SY5Y cells treated with Dimebon had an increased survival rate as compared to untreated cells. In conclusion, these data demonstrate that Dimebon enhances mitochondrial function both in the absence and presence of stress and Dimebon-treated cells are partially protected to maintain cell viability. |
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Authors:
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Shouting Zhang; Louise Hedskog; Camilla A Hansson Petersen; Bengt Winblad; Maria Ankarcrona |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of Alzheimer's disease : JAD Volume: 21 ISSN: 1875-8908 ISO Abbreviation: J. Alzheimers Dis. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-08-24 Completed Date: 2010-12-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9814863 Medline TA: J Alzheimers Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 389-402 Citation Subset: IM |
Affiliation:
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KI-Alzheimer's Disease Research Center, Karolinska Institutet, Department of Neurobiology, Care Sciences and Society (NVS), Novum, Stockholm, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Apoptosis / drug effects*, physiology Blood Proteins / pharmacology Calcium / metabolism Cell Differentiation / drug effects, physiology Cell Line, Tumor DNA, Mitochondrial / genetics Gene Dosage / drug effects Humans Indoles / pharmacology* Membrane Potential, Mitochondrial / drug effects, physiology Mice Mitochondria / drug effects*, physiology Neuroblastoma Neurons / cytology, drug effects*, physiology Neuroprotective Agents / pharmacology* Tretinoin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Blood Proteins; 0/DNA, Mitochondrial; 0/Indoles; 0/Neuroprotective Agents; 0/glucosylated serum protein; 302-79-4/Tretinoin; 3613-73-8/dimebolin; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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