Document Detail


Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death.
MedLine Citation:
PMID:  20555134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shouting Zhang; Louise Hedskog; Camilla A Hansson Petersen; Bengt Winblad; Maria Ankarcrona
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  21     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2010  
Date Detail:
Created Date:  2010-08-24     Completed Date:  2010-12-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  389-402     Citation Subset:  IM    
Affiliation:
KI-Alzheimer's Disease Research Center, Karolinska Institutet, Department of Neurobiology, Care Sciences and Society (NVS), Novum, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / 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:
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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