Mitochondrial dysfunction and Alzheimer's disease

Maruszak, Aleksandra; Żekanowski, Cezary

doi:10.1016/j.pnpbp.2010.07.004

Cited by 107 publications

(65 citation statements)

References 190 publications

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“…Accumulated evidence has shown a crucial role of mitochondrial dysfunction in patients with Alzheimer's disease [17]. Furthermore, several serine proteases have been shown to be concerned with Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 99%

Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer’s disease

et al. 2010

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HtrA2/Omi is a mitochondrial serine protease that promotes apoptotic processes, and this study investigated whether the abnormal immunoexpression of HtrA2/Omi occurs in patients with Alzheimer's disease. We prepared autopsied brains from seven control individuals and seven patients with Alzheimer's disease, and then carried out immunohistochemical studies on HtrA2/Omi using formalin-fixed, paraffin-embedded sections from all of these cases. In the cerebral cortex and hippocampus from the cases of Alzheimer's disease, densely accumulated HtrA2/Omi immunoreactivity was scattered, both intracellularly and extracellularly. Double immunofluorescence analyses showed the partial localization of HtrA2/Omi immunoreactivity in amyloid β-peptide-immunopositive senile plaques and phosphorylated τ-immunopositive neurofibrillary tangles. These results suggest that HtrA2/Omi may be partially associated with the pathogenesis of Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer’s disease

et al. 2010

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“…However, the metabolism of energy production is depleted in AD, provoking reductions in the cerebral metabolic rate of glucose [67] and mitochondrial dysfunction [3]. The low glucose consumption produces high levels of this compound in AD, as have been found in both ESI + and ESI − analysis, using polar and lipophilic extracts.…”

Section: Hypometabolismmentioning

confidence: 91%

“…Many heterogeneous cellular processes have been associated with pathological alterations in the brain of patients with Alzheimer's disease, such as β-amyloid deposition and hyperphosphorylation of τ protein [1], oxidative stress [2], mitochondrial dysfunction [3], metal dyshomeostasis [4], lipid dysregulation [5], and others. For this reason, metabolomic approaches, which provide the simultaneous measure of many untargeted metabolites, may have a high potential in the study of this multifunctional disease.…”

Section: Introductionmentioning

confidence: 99%

Using direct infusion mass spectrometry for serum metabolomics in Alzheimer’s disease

2014

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Currently, there is no cure for Alzheimer's disease and early diagnosis is very difficult, since no biomarkers have been established with the necessary reliability and specificity. For the discovery of new biomarkers, the application of omics is emerging, especially metabolomics based on the use of mass spectrometry. In this work, an analytical approach based on direct infusion electrospray mass spectrometry was applied for the first time to blood serum samples in order to elucidate discriminant metabolites. Complementary methodologies of extraction and mass spectrometry analysis were employed for comprehensive metabolic fingerprinting. Finally, the application of multivariate statistical tools allowed us to discriminate Alzheimer patients and healthy controls, and identify some compounds as potential markers of disease. This approach provided a global vision of disease, given that some important metabolic pathways could be studied, such as membrane destabilization processes, oxidative stress, hypometabolism, or neurotransmission alterations. Most remarkable results are the high levels of phospholipids containing saturated fatty acids, respectively, polyunsaturated ones and the high concentration of whole free fatty acids in Alzheimer's serum samples. Thus, these results represent an interesting approximation to understand the pathogenesis of disease and the identification of potential biomarkers.

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“…Mitochondria are the primary producers and targets of intracellular free radicals, and mitochondrial dysfunction has been postulated to be a contributing factor in the pathogenesis of autism and numerous other neurological disorders [64][65][66][67]. In a lymphoblastoid cell model, we previously demonstrated that the GSH/GSSG redox ratio in mitochondria was significantly lower in autism compared to control cells and was associated with a significantly lower mitochondrial membrane potential after nitrosative stress [16].…”

Section: Discussionmentioning

confidence: 98%

Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alterations in CNS Development

James¹

2012

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) 2012 REPORT TYPE Final DATES COVERED (From -To) TITLE AND SUBTITLE Redox Abnormalities as a Vulnerability Phenotype for Autism 5a. CONTRACT NUMBERand Related Alterations in CNS Development 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER AUTHOR(S)Sandra Jill James, Ph.D.5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERArkansas Children's Hospital Research Institute Little Rock, AR 72202 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel CommandFort Detrick, MD 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACT:We hypothesize that low systemic redox potential (GSH/GSSG; cysteine/cystine) reflects a vulnerability phenotype that is associated with regressive autism and is predictive of the risk of developing autism. The redox vulnerability phenotype is associated with epigenetic alterations in primary immune cells that may be reversible with restoration of intracellular redox potential. The hypothesis predicts that children with regressive autism and high risk (developmentally-delayed) children who are subsequently diagnosed with autism will exhibit lower redox potential compared to age-matched unaffected control children. It also predicts that low redox potential from these children will be associated with epigenetic modifications in DNA methylation and histone acetylation/methylation that are reversible with treatment to restore redox potential. In Aim 1 we will determine whether redox potential in immune cells can be used as a biomarker for regressive autism and whether it is predictive of the subsequent diagnosis of autism. We will also evaluate immune redox potential from high risk developmentally delayed children to determine whether redox status is predictive of subsequent development of autism. In Aim 2, we will determine whether immune cells from autistic children are associated with altered cytokine patterns,...

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Mitochondrial dysfunction and Alzheimer's disease

Cited by 107 publications

References 190 publications

Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer’s disease

Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer’s disease

Using direct infusion mass spectrometry for serum metabolomics in Alzheimer’s disease

Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alterations in CNS Development

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