Evaluation of respiratory chain activity in lymphocytes of patients with Alzheimer disease

Feldhaus, Pollyana; Fraga, Daiane B.; Ghedim, Fernando V.; Luca, Renata D. De; Bruna, T; Heluany, Matheus; Matos, Maria Paula; Ferreira, Gabriela K.; Jeremias, Isabela C.; Heluany, Claudia Cipriano Vidal; Streck, Emílio L.; Zugno, Alexandra I.

doi:10.1007/s11011-011-9253-y

Cited by 26 publications

(18 citation statements)

References 60 publications

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“…ETC activities of human lymphocytes were evaluated in AD patients, and increased complexes II and IV activities were observed; this might be a compensatory mechanism to supply the energy [74]. Evidences of ETC dysfunctions in AD are summarized in Table 1.…”

Section: Impairment Of Etc In Admentioning

confidence: 99%

Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease

Hroudová

Singh

Fišar

2014

BioMed Research International

258

130

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Mitochondrial dysfunctions are supposed to be responsible for many neurodegenerative diseases dominating in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD. Structurally and functionally damaged mitochondria do not produce sufficient ATP and are more prominent in producing proapoptotic factors and reactive oxygen species (ROS), and this can be an early stage of several mitochondrial disorders, including neurodegenerative diseases. Mitochondrial dysfunctions may be caused by both mutations in mitochondrial or nuclear DNA that code mitochondrial components and by environmental causes. In the following review, common aspects of mitochondrial impairment concerned about neurodegenerative diseases are summarized including ROS production, impaired mitochondrial dynamics, and apoptosis. Also, damaged function of electron transport chain complexes and interactions between pathological proteins and mitochondria are described for AD particularly and marginally for PD and HD.

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Section: Impairment Of Etc In Admentioning

confidence: 99%

Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease

Hroudová

Singh

Fišar

2014

BioMed Research International

258

130

View full text Add to dashboard Cite

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“…Additionally, the prevalence of AD increases exponentially with age in people 65 or older (Hansson et al, 2006). The disease is symptomatically characterized by progressive memory deficits, cognitive impairments, and personality changes, which can be attributed to deteriorating synaptic function and the subsequent loss of neurons in vulnerable regions of the brain, including the neocortex, the limbic system, and the subcortical regions (Fassbender et al, 2001). From a histopathological view, AD is characterized by senile plaques and neurofibrillary tangles (NFT) in the medial temporal lobe and cortical areas of the brain (Hansson et al, 2006).…”

Section: Alzheimer’s Disease – Unlimited Cost But Limited Remedymentioning

confidence: 99%

Shift in brain metabolism in late onset Alzheimer’s disease: Implications for biomarkers and therapeutic interventions

Yao¹,

Rettberg²,

Klosinski³

et al. 2011

Molecular Aspects of Medicine

109

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Alzheimer’s is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised mitochondrial bioenergetics lead to over-production and mitochondrial accumulation of β-amyloid coupled with oxidative stress to cause a shift in brain metabolic profile from glucose-driven bioenergetics towards a compensatory, but less efficient, ketogenic pathway. We propose that the compensatory shift from a primarily aerobic glycolysis pathway to a ketogenic/fatty acid β-oxidation pathway eventually leads to white matter degeneration. The essential role of mitochondrial bioenergetics and the unique trajectory of compensatory metabolic adaptations in brain enable a bioenergetic-centric strategy for development of biomarkers to detect the bioenergetic shift in brain to enable early identification of people at risk for developing AD. From a therapeutic perspective, this unique trajectory of alterations in brain metabolic capacity enable disease-stage specific strategies targeting brain metabolism for disease prevention and treatment. A combination of nutraceutical and pharmaceutical intervention that enhances glucose-driven metabolic activity and potentiates mitochondrial bioenergetic function could prevent the antecedent decline in brain glucose metabolism, promote healthy aging and prevent AD. Alternatively, during the prodromal incipient phase of AD, sustained activation of ketogenic metabolic pathways coupled with supplement of the alternative fuel source, ketone bodies, can sustain mitochondrial bioenergetic function to prevent or delay further progression of the disease.

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“…Some studies have found no effect of AD status on lymphocyte mitochondrial activity (Molina et al, 1997), whereas a recent study showed increased activity of mitochondrial respiratory chain complexes II and IV in lymphocytes isolated from patients with AD when compared with controls (Feldhaus et al, 2011). Another study showed that although there was no baseline difference in lymphocyte mitochondrial enzyme activities between controls and AD patients, those patients who were treated with the cholinesterase inhibitor rivastigmine showed increased activity of complexes II, III, and IV, indicating that increased mitochondrial efficiency might be associated with better disease outcome.…”

Section: Clinical Implications For Biomarker Identification and Thmentioning

confidence: 99%

Estrogen Regulation of Mitochondrial Bioenergetics

Yao

Brinton

2012

Advances in Pharmacology

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Alzheimer’s disease (AD) is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised aerobic glycolysis pathway coupled with oxidative stress is first accompanied by a shift toward a ketogenic pathway that eventually progresses into fatty acid oxidation (FAO) pathways and leads to white matter degeneration and overproduction and mitochondrial accumulation of β-amyloid. Estrogen-induced signaling pathways converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis coupled with citric acid cycle-driven oxidative phosphorylation to potentiate ATP (Adenosine triphosphate) generation. In addition to potentiated mitochondrial bioenergetics, estrogen also enhances neural survival and health through maintenance of calcium homeostasis, promotion of antioxidant defense against free radicals, efficient cholesterol trafficking, and beta amyloid clearance. Significantly, the convergence of E2 mechanisms of action onto mitochondria is also a potential point of vulnerability when activated in diseased neurons that exacerbates degeneration through increased load on dysregulated calcium homeostasis. The “healthy cell bias of estrogen action” hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. As the continuum of neurological health progresses from healthy to unhealthy, so too do the benefits of estrogen or hormone therapy.

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Evaluation of respiratory chain activity in lymphocytes of patients with Alzheimer disease

Cited by 26 publications

References 60 publications

Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease

Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease

Shift in brain metabolism in late onset Alzheimer’s disease: Implications for biomarkers and therapeutic interventions

Estrogen Regulation of Mitochondrial Bioenergetics

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