Abstract：
:Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated with an increased sensitivity to apoptosis induced by the 2 endoplasmic reticulum (ER) stressors thapsigargin and tunicamycin, but not by staurosporine (STS). Basal and ER stress-induced expression of Bip/Grp78 and C/EBP-homologous protein/GADD153 were not altered by AICD implying that AICD potentiated cell death downstream or independent of the conserved unfolded protein response (UPR). Interestingly, quantitative polymerase chain reaction analysis and reporter gene assays revealed that AICD significantly downregulated messenger RNA levels of the Alzheimer's disease susceptibility gene ApoJ/clusterin, indicating transcriptional repression. Knockdown of ApoJ/clusterin mimicked the effect of AICD on ER stress-induced apoptosis, but had no discernible effect on staurosporine-induced cell death. Our data suggest that altered levels of AICD may abolish the prosurvival function of ApoJ/clusterin and increase the susceptibility of neurons to ER stress-mediated cell death, a pathway that may contribute to the pathogenesis of Alzheimer's disease.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Kögel D,Concannon CG,Müller T,König H,Bonner C,Poeschel S,Chang S,Egensperger R,Prehn JHdoi
10.1016/j.neurobiolaging.2011.06.012subject
Has Abstractpub_date
2012-09-01 00:00:00pages
2200-9issue
9eissn
0197-4580issn
1558-1497pii
S0197-4580(11)00229-6journal_volume
33pub_type
杂志文章abstract：:The effect of aging on acquisition of a learned suppression of photopositive tendencies was studied in 1-7-week-old flies of both sexes. Flies had to choose in a T-maze between an alley leading to a lighted vial associated with an aversive stimulus, a quinine hydrochloride solution, and another alley leading to a dark...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.12.004
更新日期：2004-10-01 00:00:00
abstract：:Aging increases the likelihood of cognitive decline after negative life events such as infection or injury. We have modeled this increased vulnerability in aged (24-month-old), but otherwise unimpaired F344xBN rats. In these animals, but not in younger (3-month-old) counterparts, a single intraperitoneal injection of ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.07.015
更新日期：2012-04-01 00:00:00
abstract：:The relationship between hematological variables and the ability to perform behaviorally in two learning tests was evaluated in male F344 rats aged 22-24 months. Rats were screened for ability to meet criterion for learning one-way active avoidance in a straight runway task. Rats failing to meet criterion were given n...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)80011-f
更新日期：1995-01-01 00:00:00
abstract：:This study aimed to investigate cross-sectional and longitudinal changes of regional cerebral blood flow (rCBF) in preclinical dementia using single photon emission computed tomography (SPECT). SPECT and cognitive function were investigated in 39 mild cognitive impairment (MCI) subjects and 20 age-matched controls. Al...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.05.017
更新日期：2007-07-01 00:00:00
abstract：:Large repeat expansions in the C9orf72 gene were recently reported to be a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Given some of the clinical and pathologic overlap between these 2 diseases and Parkinson's disease, we sought to evaluate the presence of these expansions in a c...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.11.025
更新日期：2013-06-01 00:00:00
abstract：:Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop β-amyloid (Aβ) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associate...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.01.139
更新日期：2014-07-01 00:00:00
abstract：:Sex differences in cerebral white matter (WM) aging have been debated extensively over the past 2 decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on WM microstructure differ between sexes. Artery elasticity via carotid artery compliance (CAC) and WM diffusion ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.02.012
更新日期：2018-06-01 00:00:00
abstract：:Using resting state (RS) functional magnetic resonance imaging and independent component analysis, the integrity of brain networks related to cognition and behavior was investigated in 20 nondemented patients with amyotrophic lateral sclerosis (ALS). The association between RS functional connectivity and executive fun...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.04.015
更新日期：2013-02-01 00:00:00
abstract：:We have used structural equation models to explicitly distinguish functional status and therefore "dementia-relevant" variance in cognitive task performance (i.e., "δ" for dementia). Our approach is modular and can be directed to other targets. In this analysis, we construct a δ ortholog representing the "cognitive co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.04.003
更新日期：2015-07-01 00:00:00
abstract：:The methionine/valine (M/V) polymorphism at codon 129 within the prion protein gene (PRNP) represents a known risk factor for Creutzfeldt-Jakob disease (CJD). Few authors reported also the effects of this polymorphism on the risk of Alzheimer's disease (AD), although with controversial results. To better clarify this ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,meta分析
doi：10.1016/j.neurobiolaging.2005.05.025
更新日期：2006-05-01 00:00:00
abstract：:Our objective was to examine associations between glucose metabolism, as measured by (18)F-fluorodeoxyglucose positron emission tomography (FDG PET), and age and to evaluate the impact of carriage of an apolipoprotein E (APOE) ε4 allele on glucose metabolism and on the associations between glucose metabolism and age. ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.006
更新日期：2014-09-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 pat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.01.004
更新日期：2017-05-01 00:00:00
abstract：:RACK1 (receptor for activated C-kinase 1), an anchoring protein that shuttles activated PKC to cellular membranes, plays an important role in PKC-mediated signal transduction pathways. A significant loss of RACK1 has been found in the brain of aging animals and Alzheimer's disease (AD) patients, which implicates the p...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.10.017
更新日期：2011-10-01 00:00:00
abstract：:The growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg SC) was studied in young and elderly normal subjects as well as in patients with dementia of the Alzheimer type (DAT) and controls matched for age, gender and Quetelet index. The GH response was significantly decrease...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(89)90055-9
更新日期：1989-05-01 00:00:00
abstract：:Astrocytes and microglia from cerebral cortex of 3-, 6-, 12-, and 24-month-old F344 male rat donors showed progressively greater proliferation during primary culture. Microglia from aging donor brains exhibited an amoeboid-like morphology and express antigens characteristic of an activated state (e.g., major histocomp...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00169-3
更新日期：1998-01-01 00:00:00
abstract：:Insertion and deletion variants (indels) within poly glycine tracts of fused in sarcoma (FUS) were initially reported as causative of disease in amyotrophic lateral sclerosis (ALS). Subsequent studies identified similar indels in controls and suggested that these indels may confer susceptibility to ALS. We aimed to el...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.09.029
更新日期：2012-02-01 00:00:00
abstract：:Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In thi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.06.019
更新日期：2020-11-01 00:00:00
abstract：:G4C2 hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). In this study, we investigated the presence of the G4C2 repeat expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.01.007
更新日期：2018-06-01 00:00:00
abstract：:The substantia innominata (SI) contains the nucleus basalis of Meynert, which provides the major cholinergic innervation to the entire cortical mantel and the amygdala; degeneration of nucleus basalis neurons correlates with cognitive decline in Alzheimer's disease (AD). However, whether SI atrophy occurs in individua...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.11.006
更新日期：2011-10-01 00:00:00
abstract：:Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.08.011
更新日期：2009-05-01 00:00:00
abstract：:Although neuroactive steroids exert neuroprotective actions in different experimental models of neurodegenerative diseases, including those of Alzheimer's disease (AD), their relationships with aged related physiologic and pathologic brain changes remain to be clarified. In this study the levels of pregnenolone, dehyd...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.10.007
更新日期：2013-04-01 00:00:00
abstract：:We examined whether cognitive reserve (CR) impacts level of, or rate of change in, biomarkers of Alzheimer's disease (AD) and small-vessel cerebrovascular disease in >250 individuals who were cognitively normal and middle-aged and older at the baseline. The four primary biomarker categories commonly examined in studie...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.12.003
更新日期：2020-04-01 00:00:00
abstract：:Reduced excitability, due to an increase in the slow afterhyperpolarization (and its underlying current sI(AHP)), occurs in CA1 pyramidal cells in aged cognitively-impaired, but not cognitively-unimpaired, rodents. We sought to determine whether similar age-related changes in the sI(AHP) occur in pyramidal cells in th...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.07.002
更新日期：2012-06-01 00:00:00
abstract：:The adaption of movement to changes in the environment varies across life span. Recent evidence has linked motor adaptation and its reduction with age to differences in "explicit" learning processes. We examine differences in brain structure and cognition underlying motor adaptation in a population-based cohort (n = 3...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.02.016
更新日期：2020-06-01 00:00:00
abstract：:Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidatio...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.03.005
更新日期：2016-07-01 00:00:00
abstract：:Chronic treatment (21 days) with phosphatidylserine (BC-PS) partially restored the reduced density of muscarinic cholinergic receptors in several regions of the aged (18 months) mouse brain. The effect was similar whether 3H-QNB or 3H-NMS was used as radioligand. The affinity of both radioligands was not altered by BC...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90007-k
更新日期：1992-01-01 00:00:00
abstract：:Evidence accumulates suggesting a complex interplay between neurodegenerative processes and serotonergic neurotransmission. We have previously reported an overexpression of serotonin 5-HT1A receptors (5-HT(1A)R) after intrahippocampal injections of amyloid-beta 1-40 (Aβ40) fibrils in rats. This serotonergic reactivity...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.12.008
更新日期：2016-04-01 00:00:00
abstract：:Individuals with Down syndrome (DS) overexpress many genes on chromosome 21 due to trisomy and have high risk of dementia due to the Alzheimer's disease (AD) neuropathology. However, there is a wide range of phenotypic differences (e.g., age at onset of AD, amyloid β levels) among adults with DS, suggesting the import...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.04.018
更新日期：2017-08-01 00:00:00
abstract：:Similar to elderly humans, aged outbred Long-Evans rats exhibit individual differences in memory abilities, including a subset of aged rats that maintain memory function on par with young adults. Such individuals provide a basis for investigating mechanisms of resilience to age-related decline. The present study exami...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.12.015
更新日期：2019-04-01 00:00:00
abstract：:Insomnia, daytime sleepiness, and nocturnal wandering, so common in the elderly, are caused largely by two specific pathophysiologic processes. Sleep apnea is a condition where respiration pauses during sleep, leading to arousal. Sleep apnea is due either to obstruction in the throat or failure of the central respirat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(82)90021-5
更新日期：1982-01-01 00:00:00
