Abstract：
:Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant presenilin-1 (mPS1). CQ induced vacuole formation and cell death in adult retinal pigment epithelial (ARPE-19) cells, but co-treatment with ClioQ attenuated CQ-associated toxicity in a zinc-dependent manner. Increases in lysosome dilation and blockage of autophagic flux by CQ were also markedly attenuated by ClioQ treatment. Interestingly, CQ increased lysosomal pH in amyloid precursor protein (APP)/mPS1-expressing Chinese hamster ovary 7WΔE9 (CHO-7WΔE9) cell line, and ClioQ partially re-acidified lysosomes. Furthermore, accumulation of amyloid-β (Aβ) oligomers in CHO-7WΔE9 cells was markedly attenuated by ClioQ. Moreover, intracellular accumulation of exogenously applied fluorescein isothiocyanate-conjugated Aβ(1-42) was also increased by CQ but was returned to control levels by ClioQ. These results suggest that modulation of lysosomal functions by manipulating lysosomal zinc levels may be a useful strategy for clearing intracellular Aβ oligomers.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Seo BR,Lee SJ,Cho KS,Yoon YH,Koh JYdoi
10.1016/j.neurobiolaging.2015.09.006subject
Has Abstractpub_date
2015-12-01 00:00:00pages
3228-3238issue
12eissn
0197-4580issn
1558-1497pii
S0197-4580(15)00452-2journal_volume
36pub_type
杂志文章abstract：:A variety of studies have shown an effect of estrogen on dopamine function and suggest that estrogen may modulate central dopaminergic activity. Positron emission tomography (PET) and the dopamine metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate dopaminergic function in the frontal cortex and ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00323-2
更新日期：2002-05-01 00:00:00
abstract：:Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, accordi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.02.010
更新日期：2017-06-01 00:00:00
abstract：:An experiment was performed to test the ability of Centrophenoxine to reduce the amount of lipofuscin (age pigment) in the retinal pigment epithelium (RPE) of aged rhesus monkeys. Centrophenoxine is reputed to have this action in neurons of lower mammals. Quantitative electron microscopic analysis was performed on sec...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(86)90148-x
更新日期：1986-03-01 00:00:00
abstract：:Cortisol and ACTH exhibit circadian rhythmicity, peaking in the early morning. These peaks are associated with increased activity and alertness. We sought to determine whether self-reported daily rhythms predict outcome of a.m. and p.m. CRH challenge in elderly subjects. We surveyed 96 elderly subjects to determine da...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90029-b
更新日期：1993-01-01 00:00:00
abstract：:Brain-specific glutathione S-transferase Mu 3 (GSTM3) colocalizes with amyloid-beta plaques in Alzheimer's disease (AD). A functional polymorphism rs7483 in GSTM3 may contribute to the decrease in GSTM3 expression in AD. The association of the rs7483 SNP with late-onset AD and mild cognitive impairment (MCI) was evalu...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.03.007
更新日期：2010-01-01 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：:Pathologic expansion of the G4C2 repeat in C9orf72 is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To evaluate the frequency of the G4C2 expansion in a Latin American cohort of FTD and ALS patients, we used a 2-step genotyping strategy. For FTD, we observed an overal...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.001
更新日期：2016-04-01 00:00:00
abstract：:In the last decade, functional magnetic resonance imaging (fMRI) has emerged as a tool to study changes in brain function associated with a genetic risk for Alzheimer's disease (AD), with a particular focus on the effects of the APOE-ε4 allele. This review compiles the existing literature concerning the effects of APO...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2010.03.009
更新日期：2012-02-01 00:00:00
abstract：:The first hypothesis free genome wide association study on cognition recently revealed the thus far unknown association of a single nucleotide polymorphism (SNP) of the KIBRA gene with episodic memory in healthy young and middle aged volunteers. Here, we report the first independent replication of this finding in an i...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.02.001
更新日期：2008-07-01 00:00:00
abstract：:Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.029
更新日期：2012-05-01 00:00:00
abstract：:Despite very numerous studies on Alzheimer's disease (AD), especially on amyloid plaques and neurofibrillary tangles, little information has been obtained thus on the causes of the disease. Evidence is described here that implicates firstly herpes simplex virus type 1 (HSV1) as a strong risk factor when it is present ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2003.12.021
更新日期：2004-05-01 00:00:00
abstract：:We present a fresh approach to evaluating association with candidate genes and cognitive change by testing association for parameters describing individual growth curves from twins. Moderate genetic influences on memory in aging adults has been shown in quantitative genetic studies. A recently reported, association of...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.12.009
更新日期：2006-01-01 00:00:00
abstract：:Degeneration of septal neurons in Alzheimer's disease (AD) results in abnormal information processing at cortical circuits and consequent brain dysfunction. The septum modulates the activity of hippocampal and cortical circuits and is crucial to the initiation and occurrence of oscillatory activities such as the hippo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.05.006
更新日期：2010-01-01 00:00:00
abstract：:Although peripheral nerves are capable of regeneration, advanced age decreases the potential for functional recovery after injury. The cellular mechanisms for this are not currently understood. Here, we performed sciatic nerve grafting with young (2 months old) and aged (18 months old) Brown-Norway male rats, in which...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.05.004
更新日期：2016-09-01 00:00:00
abstract：:The knowledge base of nutrition and the brain is steadily expanding. Much of the research is aimed at ways to protect the brain from damage. In adults, the major causes of brain damage are aging and dementia. The most prominent dementia, and the condition that grabs the most public attention, is Alzheimer's disease. T...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2014.02.029
更新日期：2014-09-01 00:00:00
abstract：:The ability to maintain cognitive function during aging is a complex process subject to genetic and environmental influences. Alzheimer's disease (AD) is the most common disorder causing cognitive decline among the elderly. Among those with AD, there is broad variation in the relationship between AD neuropathology and...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.11.008
更新日期：2008-04-01 00:00:00
abstract：:Differential cell death is a common feature of aging and age-related disease. In the retina, 30% of rod photoreceptors are lost over life in humans and rodents. However, studies have failed to show age-related cell death in mouse cone photoreceptors, which is surprising because cone physiological function declines wit...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.05.012
更新日期：2014-11-01 00:00:00
abstract：:In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.08.008
更新日期：2015-01-01 00:00:00
abstract：:Calmodulin (CaM) and tubulin were analyzed by radioimmunoassay in subcellular fractions prepared from cerebral cortex and striatum of aging male C57BL/6J mice. Three fractions were prepared by a new procedure: cytosol (soluble); EGTA-releasable, membrane-bound; and detergent-extractable (Triton X-100), membrane-bound ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(87)90022-4
更新日期：1987-03-01 00:00:00
abstract：:TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTL...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.04.010
更新日期：2014-10-01 00:00:00
abstract：OBJECTIVE:We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD:Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2004.03.003
更新日期：2005-02-01 00:00:00
abstract：:In Parkinson disease, wild-type alpha-synuclein accumulates during aging, whereas alpha-synuclein mutations lead to an early onset and accelerated course of the disease. The generation of new neurons is decreased in regions of neurogenesis in adult mice overexpressing wild-type human alpha-synuclein. We examined the s...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.12.016
更新日期：2008-06-01 00:00:00
abstract：:Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.02.006
更新日期：2011-06-01 00:00:00
abstract：:The 'amyloid hypothesis' has guided research into Alzheimer's disease (AD) for more than a decade. A detailed review of the relevant data led us to conclude that some data, particularly those from transgenic mice, are inconsistent with the predictions of the amyloid hypothesis. Instead, most data are consistent with t...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/s0197-4580(02)00050-7
更新日期：2002-11-01 00:00:00
abstract：:The present study investigated if a causal relation exists between serum concentrations of precursors and metabolites of cholesterol and cognitive performance in a healthy aging population. Cognitive function addressing four domains of 144 individuals (30-80 years) was tested at baseline and after 6 years of follow-up...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00061-1
更新日期：2003-01-01 00:00:00
abstract：:The definitive diagnosis of Alzheimer's disease (AD) is made at autopsy by the presence of abundant neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex, entorhinal cortex, and hippocampus. The two criteria most frequently used by neuropathologists for the diagnosis of AD over the past 12 years are...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(97)00064-x
更新日期：1997-07-01 00:00:00
abstract：:Patients with Mild Cognitive Impairment (MCI), exhibiting both working memory and olfactory deficits are likely to progress to Alzheimer's disease (AD). Targeting this pre-clinical AD population with disease modifying agents or cognitive enhancers represents the best strategy for halting or delaying the impact of this...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.11.018
更新日期：2009-09-01 00:00:00
abstract：:Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition betwee...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.05.007
更新日期：2014-11-01 00:00:00
abstract：:Synaptic density in the medial and lateral septal nuclei was examined in 3 and 24-28 months of age Fischer 344 rats. The lateral nucleus had a higher synaptic density than the medial region in both age groups. There were no statistically significant differences in synapse density in either region as a function of age,...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(91)90032-f
更新日期：1991-01-01 00:00:00
abstract：OBJECTIVE:To investigate whether cognitive function in the spectrum of normal aging to Alzheimer's disease is better reflected in MRI or EEG measures, or a combination of both. METHODS:Cognitive functions were tested in 33 elderly subjects: 10 with probable Alzheimer's disease, 11 with mild cognitive impairment and 12...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.06.006
更新日期：2007-09-01 00:00:00
