A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury.

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Abstract Text:

Alzheimer's disease (AD) is associated with beta-amyloid accumulation, oxidative stress and mitochondrial dysfunction. However, the effects of genetic mutation of AD on oxidative status and mitochondrial manganese superoxide dismutase (MnSOD) production during neuronal development are unclear. To investigate the consequences of genetic mutation of AD on oxidative damages and production of MnSOD during neuronal development, we used primary neurons from new born wild-type (WT/WT) and amyloid precursor protein (APP) (NLh/NLh) and presenilin 1 (PS1) (P264L) knock-in mice (APP/PS1) which incorporated humanized mutations in the genome. Increasing levels of oxidative damages, including protein carbonyl, 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), were accompanied by a reduction in mitochondrial membrane potential in both developing and mature APP/PS1 neurons compared with WT/WT neurons suggesting mitochondrial dysfunction under oxidative stress. Interestingly, developing APP/PS1 neurons were significantly more resistant to beta-amyloid 1-42 treatment, whereas mature APP/PS1 neurons were more vulnerable than WT/WT neurons of the same age. Consistent with the protective function of MnSOD, developing APP/PS1 neurons have increased MnSOD protein and activity, indicating an adaptive response to oxidative stress in developing neurons. In contrast, mature APP/PS1 neurons exhibited lower MnSOD levels compared with mature WT/WT neurons indicating that mature APP/PS1 neurons lost the adaptive response. Moreover, mature APP/PS1 neurons had more co-localization of MnSOD with nitrotyrosine indicating a greater inhibition of MnSOD by nitrotyrosine. Overexpression of MnSOD or addition of MnTE-2-PyP(5+) (SOD mimetic) protected against beta-amyloid-induced neuronal death and improved mitochondrial respiratory function. Together, the results demonstrate that compensatory induction of MnSOD in response to an early increase in oxidative stress protects developing neurons against beta-amyloid toxicity. However, continuing development of neurons under oxidative damage conditions may suppress the expression of MnSOD and enhance cell death in mature neurons.

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Publishing Authors By Initials

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Neuroscience

VOLUME: 153

Page Numbers: 120-30

Journal Abbreviation: Neuroscience

ISSN: 0306-4522

DAY: 7

MONTH: 02

YEAR: 2008

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7605074

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury.

AFFILIATION: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA; Faculty of Medical Technology, Mahidol University, Bangkok, Thailand 10700.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Neuroscience

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury Related Publications

• A major QTL introgressed from wild Lycopersicon hirsutum confers chilling tolerance to cultivated tomato (Lycopersicon esculentum).
• A neuronal model of Alzheimer's disease: An insight into the mechanisms of oxidative stress-mediated mitochondrial injury.
• Adjuvant radiation of bilateral postauricular keloids: an illustration of technique.
• An unusual photoactivated skin eruption. Quinidine-induced livedo reticularis.
• B cell-directed therapies for autoimmune disease and correlates of disease response and relapse.
• Chronic exposure to 12-O-tetradecanoylphorbol-13-acetate represses sod2 induction in vivo: the negative role of p50.
• Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues.
• Competing values in healthcare: balancing the (un)balanced scorecard.
• Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non-small cell lung cancer both in vitro and in vivo.
• Erratum.
• Functional genomics and ecology - a tale of two scales.
• Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells.
• NF-kappaB-associated MnSOD induction protects against beta-amyloid-induced neuronal apoptosis.
• Natural variation among Arabidopsis thaliana accessions for transcriptome response to exogenous salicylic acid.
• Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury.
• RHIOs in reverse.
• ROS and p53: A versatile partnership.
• Redox proteomic identification of oxidized cardiac proteins in adriamycin-treated mice.
• SN52, a novel nuclear factor-{kappa}B inhibitor, blocks nuclear import of RelB:p52 dimer and sensitizes prostate cancer cells to ionizing radiation.
• School-based drug prevention among at-risk adolescents: effects of ALERT plus.
• Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures.
• Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1alpha,25-dihydroxyvitamin D(3) in prostate cancer cells.
• The calm after the cytokine storm: lessons from the TGN1412 trial.
• The radiosensitization effect of parthenolide in prostate cancer cells is mediated by nuclear factor-kappaB inhibition and enhanced by the presence of PTEN.
• The role of a single-stranded nucleotide loop in transcriptional regulation of the human sod2 gene.
• Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells.
• Unilateral, linear, zosteriform epidermal nevus with acantholytic dyskeratosis.