Abstract:
:Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder among the elderly. Nmethyl- D-aspartate receptor (NMDAR) overactivation has been implicated in early synaptic dysfunction that precedes late neurodegeneration in AD. Moreover, oligomers of amyloid-beta peptide (Aβ) 1-42 are considered the most synaptotoxic forms, responsible for early cognitive deficits in AD. In this work we evaluate the role of NMDARs on Aβ-evoked neuronal dysfunction and cell death through changes in microtubule polymerization in mature hippocampal cultures. Exposure to Aβ 1-42 caused a decrease in total and polymerized levels of beta-III tubulin and polymerized alpha-tubulin, suggesting microtubule disassembly. Moreover, Aβ induced DNA fragmentation in both neuronal and non-neuronal cells. Indeed, the effects of Aβ on beta-III tubulin polymerization were significantly correlated with reduced neurite length and neuronal DNA fragmentation. Interestingly, these effects were prevented by MK-801 and memantine, suggesting a role for extrasynaptic NMDARs in Aβ toxicity, and by ifenprodil, further indicating the involvement of GluN2B-containing NMDARs. Nevertheless, exposure to Aβ did not potentiate the effects caused by selective activation of NMDARs. Data largely suggest that Aβ-induced hippocampal neuronal dysfunction occurs through NMDAR-dependent microtubule disassembly associated to neurite retraction and DNA fragmentation in mature hippocampal cells.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Mota SI,Ferreira IL,Pereira C,Oliveira CR,Rego ACdoi
10.2174/156720512802455322subject
Has Abstractpub_date
2012-09-01 00:00:00pages
844-56issue
7eissn
1567-2050issn
1875-5828pii
CAR-EPUB-20120521-20journal_volume
9pub_type
杂志文章abstract::Neurodegenerative diseases may directly affect memory performance, thus leading to functional impairments. An increasing body of evidence suggests an association between dietary intake of omega-3 fatty acids and memory functioning in animal models as well as in human studies. Recent evidence supports a potential benef...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160602235520
更新日期:2017-01-01 00:00:00
abstract::Human memory can be split into familiarity and recollection processes which contribute to different aspects of memory function. These separate processes result in different experiential states. In this review, we examine how this dominant theoretical framework can explain the subjective experience of people with Alzhe...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509788486545
更新日期:2009-06-01 00:00:00
abstract::Heme is essential for the survival of most organisms, despite the fact of being potentially toxic. This dual effect is due to the ability of the iron (Fe) atom contained within the protoporphyrin ring of the heme molecule to participate in redox reactions and exchange electrons with a variety of substrates. Therefore,...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205012666150921103304
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Recent studies have identified the correlation between dementia and certain vocal features, such as voice and speech changes. Vocal features may act as early markers of Alzheimer's disease (AD). Despite being present in non-pathological senescence and Mild Cognitive Impairment, especially in its amnesic subt...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205014666170829112439
更新日期:2018-01-01 00:00:00
abstract::The Twentieth Century witnessed tremendous advances in our understanding of neurodegenerative diseases. Not least among them were the contributions from hyperendemic foci of neurodegenerative disorders in isolated human groups worldwide, with the knowledge gained applicable to our understanding of related neurodegener...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506778249425
更新日期:2006-09-01 00:00:00
abstract::Amyloid-β protein (Aβ) accumulates in the neurons of Alzheimer's disease (AD) patients at an early stage of the disease. Recently, we found that Aβ with a toxic turn at positions 22 and 23 accumulates in neurons in AD brain. Here, we studied the accumulation of Aβ, toxic turn Aβ and high-molecular-weight Aβ oligomers ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Accumulating evidence has suggested the involvement of oxidative stress in the pathogenesis of Alzheimer's disease (AD). The main endogenous antioxidant, glutathione (GSH), has been shown to decline with ageing and in several age-related degenerative diseases, including AD. Potential options for replenishing GSH level...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205012666150302160308
更新日期:2015-01-01 00:00:00
abstract::The field of aging and dementia research is advancing rapidly toward the stage of earlier identification of clinical symptoms. Ultimately, clinicians would like to be able to identify individuals who are asymptomatic but at risk for developing dementia. In the interim, the construct of mild cognitive impairment (MCI) ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509788929237
更新日期:2009-08-01 00:00:00
abstract::In this work, we present a fully automatic computer-aided diagnosis method for the early diagnosis of the Alzheimer's disease. We study the distance between classes (labelled as normal controls and possible Alzheimer's disease) calculated in 116 regions of the brain using the Welchs's t-test. We select the regions wit...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666160415154852
更新日期:2016-01-01 00:00:00
abstract::Rigorous scientific research has identified multiple interactive mechanisms that parallel and are likely causative of the development of Alzheimer's disease (AD). Causative mechanisms include genomics, the creation of amyloid beta (Abeta), factors inhibiting the Abeta removal process, the transformation of Abeta to it...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506776383068
更新日期:2006-04-01 00:00:00
abstract::The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropatholo...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720510790691218
更新日期:2010-03-01 00:00:00
abstract::In this study, we aimed to classify MR images for recognizing Alzheimer Disease (AD) in a group of patients who were recently diagnosed by clinical history and neuropsychiatric exams by using non-biased machine-learning techniques. T1 weighted MRI scans of 31 patients with probable AD and 31 age- and gender-matched co...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512802455359
更新日期:2012-09-01 00:00:00
abstract::The definite diagnosis of Alzheimer's disease (AD) is based on the detection of beta amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) - which are the pathological hallmarks of the disease- in the postmortem brains. Although regional Cerebral Blood Flow (rCBF) and Cerebral Glucose Metabolism (CGM) abnormalities ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720510792231757
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:The longitudinal change of neuropsychological tests (NPTs) in treated Alzheimer's disease (AD) is essential to understand the interplay of a therapeutic response from medication and a disease decline due to degenerative processes. The aim of our study is to investigate the annual cognitive progression as mea...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205014666171010112518
更新日期:2018-03-14 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720501209151019105647
更新日期:2015-01-01 00:00:00
abstract::Features of autoimmunity have been associated with both Alzheimer's disease (AD) and with diabetes. In both diseases high levels of advanced glycation end products (AGEs) and their receptor (RAGE) have been detected in tissues and in the circulation. In addition high titers of antibodies directed against a RAGE-like p...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720506777632899
更新日期:2006-07-01 00:00:00
abstract::Alzheimer's disease is a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary tangles. Cholinergic dysfunction is also a main pathological feature of the disease. Nevertheless, the links between cholinergic dysfunction and neuropathological hallmarks of Alzheimer's are still unknown. In the...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720509787602843
更新日期:2009-04-01 00:00:00
abstract::The aggregation of the microtubule-associated protein tau into paired-helical filaments is the defining characteristic of the tauopathies. It has become apparent that the hyperphosphorylation of tau likely plays a role in the aggregation process and thus strategies to reduce tau phosphorylation are generating wide int...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509789207967
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:The USA National Task Group (NTG) guidelines advocate the use of an adapted version of Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) for dementia screening of individuals with Down syndrome (DS) and with other forms of ID (non-DS). OBJECTIVE:In order to meet these ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/1567205014666170117094757
更新日期:2017-01-01 00:00:00
abstract::As the average ages of North Americans and Europeans continue to rise; similarly the incidence of "old age" associated illnesses likewise increases. Most notably among these ailments are conditions linked to dementia-related neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and st...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507781788873
更新日期:2007-09-01 00:00:00
abstract::In the present study we set up a model of slow progression of neuronal injury by exposing organotypic hippocampal cultures to a low concentration of Amyloid β (25-35) peptide (Aβ, 2 μM) to analyze the time-related effects of 17-β estradiol (17β-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition o...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666160125113509
更新日期:2016-01-01 00:00:00
abstract::The first reports of disorders that in terms of cognitive and behavioral symptoms resemble frontotemporal dementia (FTD) and in terms of motor symptoms resemble amyotrophic lateral sclerosis (ALS) bring us back to the second half of the 1800s. Over the last 150 years, and especially in the last two decades, there has ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720511795563700
更新日期:2011-05-01 00:00:00
abstract::This article presents a new paradigm of Artificial Neural Networks (ANNs): the Auto-Contractive Maps (Auto-CM). The Auto-CM differ from the traditional ANNs under many viewpoints: the Auto-CM start their learning task without a random initialization of their weights, they meet their convergence criterion when all thei...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720508785908928
更新日期:2008-10-01 00:00:00
abstract::To search for potential mechanism that might alter synaptic transmission following Abeta increase we have examined the presynaptic component of transmitter release. As parameters of synaptic transmission that might underlie presynaptic mechanisms, we have used paired-pulse facilitation (PPF), post-tetanic potentiation...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205053585936
更新日期:2005-04-01 00:00:00
abstract::Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (Aβ) peptide production underlie the universal development of Alzheimer's disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720501301151207100616
更新日期:2016-01-01 00:00:00
abstract::Identification of genes and pathways that alter lifespan has allowed for new insights into factors that control the aging process as well as disease. While strong molecular links exist between aging and metabolism, we hypothesize that targeting the mechanisms involved in aging will also give rise to therapeutics that ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362038
更新日期:2007-04-01 00:00:00
abstract::Altered progranulin levels play a major role in neurodegenerative diseases, like Alzheimer's dementia (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), even in the absence of GRN mutations. Increasing progranulin levels could hereby provide a novel treatment strategy. However, knowledge on p...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666160314151247
更新日期:2016-01-01 00:00:00
abstract::Metabolic syndrome (MetS), i.e., meeting criteria for any three of the following: hyperglycemia, hypertension, hypertriglyceridemia, low high-density lipoprotein and/or abdominal obesity, is associated with negative health outcomes. For example, MetS negatively impacts cognition; however, less is known about increment...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150701102325
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:The lack of diagnostic tools and disease-modifying treatments against Alzheimer's disease (AD) and related disorders, collectively known as tauopathies, has led to a socioeconomic burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome changes that could help us understand...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180813152043
更新日期:2018-01-01 00:00:00
abstract::The occurrence of a plaque-dependent inflammation in Alzheimer's disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795255982
更新日期:2011-03-01 00:00:00