Abstract：
:Mounting evidence indicates increased susceptibility to cell death and increased oxidative damage as common features in neurons from sporadic Alzheimer's disease (AD) patients but also from familial AD (FAD) cases. Autosomal dominant forms of FAD are caused by mutations of the amyloid precursor protein (APP) gene and by mutations of the genes encoding for presenilin 1 or presenilin 2 (PS1/2). We investigated the effect of the Swedish APP double mutation (APPsw) on oxidative stress-induced cell death mechanisms in PC12 cells. This mutation results in from three- to sixfold increased beta-amyloid (Abeta) production compared with wild-type APP (APPwt). Because APPsw cells secrete low Abeta levels similar to the situation in FAD brains, our cell model represents a very suitable approach to elucidate the AD-specific cell death pathways under more likely physiological conditions. We found that APPsw-bearing cells show decreased mitochondrial membrane potential after exposure to hydrogen peroxide. In addition, activity of the executor caspase 3 after treatment with hydrogen peroxide was elevated in APPsw cells, which seems to be the result of an enhanced activation of both intrinsic and extrinsic apoptosis pathways. Our findings provide evidence that the massive neurodegeneration in early age of FAD patients could be a consequence of an increased vulnerability of neurons by mitochondrial abnormalities resulting in activation of different apoptotic pathways as a consequence to elevated oxidative stress levels. Finally, we propose a hypothetical sequence of the pathogenic steps linking sporadic AD, FAD, Abeta production, mitochondrial dysfunction with caspase pathway, and neuronal loss.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Eckert A,Marques CA,Keil U,Schüssel K,Müller WEdoi
10.1196/annals.1299.113subject
Has Abstractpub_date
2003-12-01 00:00:00pages
604-9eissn
0077-8923issn
1749-6632journal_volume
1010pub_type
杂志文章,评审abstract：:Rewards can be viewed as probability distributions of reward values. Besides expected (mean) value, a key parameter of such distributions is variance (or standard deviation), which constitutes a measure of risk. Single neurons in orbitofrontal cortex signal risk mostly separately from value. Comparable risk signals in...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2011.06256.x
更新日期：2011-12-01 00:00:00
abstract：:Choir singing is positively associated with well-being and quality of life, and requires the coordination of physiological systems within and across individuals. Informed by models of interpersonal action coordination, we delineate the network topography of choir singing by analyzing cross-frequency couplings and with...
journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1976.tb47717.x
更新日期：1976-01-01 00:00:00
abstract：:Adolescence and emerging adulthood form a critical time period for the achievement of optimal health and nutrition across all stages of the life course. We undertook a review of published literature and global data repositories for information on nutrition levels, trends, and patterns among young people aged 10-24 yea...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,meta分析,评审
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abstract：:The liver is morphologically and functionally modulated by sex hormones. Long-term use of oral contraceptives (OCs) and anabolic androgenic steroids (AASs) can induce both benign (hemangioma, adenoma, and focal nodular hyperplasia [FNH]) and malignant (hepatocellular carcinoma [HCC]) hepatocellular tumors. Hepatic ade...
journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1996.tb26724.x
更新日期：1996-08-15 00:00:00
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1996.tb33306.x
更新日期：1996-11-18 00:00:00
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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更新日期：2007-10-01 00:00:00
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journal_title：Annals of the New York Academy of Sciences
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更新日期：2006-11-01 00:00:00
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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更新日期：1992-04-30 00:00:00
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1994.tb21759.x
更新日期：1994-09-30 00:00:00
abstract：:Curcumin (Cur), the golden yellow phenolic compound in turmeric, is well studied for its medicinal properties. In the current investigation, Cur dissolved using sodium hydroxide solution (CurNa) was tested for in vitro complement inhibitory activity and compared with rosmarinic acid (RA) and quercetin (Qur) dissolved ...
journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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更新日期：2001-06-01 00:00:00
abstract：:Cerebrovascular deposition of amyloid is a frequent observation in Alzheimer's disease patients. It can also be detected sporadically in normal aged individuals and is further found in familial diseases linked to specific gene mutations. The source and mechanism of this pathology are still unknown. It has been suggest...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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更新日期：2000-04-01 00:00:00
abstract：:Despite neuropathological and electrophysiological evidence for the involvement of parahippocampal structures in temporal lobe epilepsy (TLE), little attention has been paid to morphometric changes in these structures, and the relation of these changes to TLE. We performed high-resolution MRI volumetric analysis to ex...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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更新日期：2000-06-01 00:00:00
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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更新日期：1999-01-01 00:00:00
abstract：:The aim of this prospective study was to assess the prevalence of antiphospholipid antibodies (aPL) in women who had undergone in vitro fertilization (IVF) and the relationship between aPL and IVF outcome. A total of 101 infertile women with at least three unsuccessful IVF attempts were consecutively included in this ...
journal_title：Annals of the New York Academy of Sciences
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更新日期：2007-06-01 00:00:00
abstract：:Using a newly developed algorithm in conjunction with the front tracking scheme, we have evaluated the transport associated with a deformable bubble moving in a tube in the presence of a soluble or an insoluble surfactant. Such evaluations are useful to the understanding of gas embolism--a common syndrome for decompre...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
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更新日期：2006-09-01 00:00:00
abstract：:Pulmonary sarcoidosis is a disease characterized by increased numbers of T lymphocytes within the alveolar structures and the consequent spontaneous release of a variety of mediators relevant to the pathogenesis of this disorder. This phenomenon is associated with a different expansion of the T cell subpopulations pre...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1986.tb18488.x
更新日期：1986-01-01 00:00:00
abstract：:Our molecular studies have revealed the existence of a large number of different subunits or subtypes for the NMDA and metabotropic glutamate receptors. The individual receptors show functional variabilities and distinct expression patterns in the CNS. The NMDA receptors belong to the ligand-gated ion channel family a...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1993.tb38050.x
更新日期：1993-12-20 00:00:00
