Abstract:
:Amyloid beta (Aβ) binding alcohol dehydrogenase (ABAD) is a cellular cofactor for promoting (Aβ)-mediated mitochondrial and neuronal dysfunction, and cognitive decline in transgenic Alzheimer's disease (AD) mouse models. Targeting mitochondrial ABAD may represent a novel therapeutic strategy against AD. Here, we report the biological activity of small molecule ABAD inhibitors. Using in vitro surface plasmon resonance (SPR) studies, we synthesized compounds with strong binding affinities for ABAD. Further, these ABAD inhibitors (ABAD-4a and 4b) reduced ABAD enzyme activity and administration of phosphonate derivatives of ABAD inhibitors antagonized calcium-mediated mitochondrial swelling. Importantly, these compounds also abolished Aβ-induced mitochondrial dysfunction as shown by increased cytochrome c oxidase activity and adenosine-5'-triphosphate levels, suggesting protective mitochondrial function effects of these synthesized compounds. Thus, these compounds are potential candidates for further pharmacologic development to target ABAD to improve mitochondrial function.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Valaasani KR,Sun Q,Hu G,Li J,Du F,Guo Y,Carlson EA,Gan X,Yan SSdoi
10.2174/1567205011666140130150108subject
Has Abstractpub_date
2014-02-01 00:00:00pages
128-36issue
2eissn
1567-2050issn
1875-5828pii
CAR-EPUB-58904journal_volume
11pub_type
杂志文章abstract:BACKGROUND:Previous work designed a network-based protocol of cognitive training. This programme exploits a mechanism of induced task-oriented co-activation of multiple regions that are part of the default mode network (DMN), to induce functional rewiring and increased functional connectivity within this network. OBJE...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666171212103323
更新日期:2018-01-01 00:00:00
abstract::Rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show an increase in hippocampal neurogenesis. We show that both environmental enrichment, as well as performance in the Morris water maze, a hippocampal-dependent learning task, leads to an increase in local VEGF expres...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506775697133
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:To study the prevalence of cognitive impairment and dementia in communitydwelling Malays from Singapore; and to examine differences in prevalence among Chinese and Malays. METHODS:Subjects (≥ 60 years) - drawn from the Malay component of the on-going multiethnic Epidemiology of Dementia in Singapore study - ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666151002123813
更新日期:2017-01-01 00:00:00
abstract::Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510793499075
更新日期:2010-11-01 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::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::Mitochondrial dysfunction has been implicated in causing metabolic abnormalities in Alzheimer's disease (AD). The searches for mitochondrial DNA variants associated with AD susceptibility have generated conflicting results. The age-related accumulation of somatic mitochondrial DNA deletion has been suggested to play a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506779025215
更新日期:2006-12-01 00:00:00
abstract::Accumulating evidence has suggested the involvement of oxidative stress in the pathogenesis of Alzheimer's disease (AD).The main endogenousantioxidant,glutathione (GSH),has been shown to decline with ageing and in several age-related degenerative diseases, including AD. Potential options for replenishing GSH levels as...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2015-03-24 00:00:00
abstract:BACKGROUND:Impairment in instrumental activities of daily living (IADL) emerges in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. Some IADL scales are sensitive to early deficits in MCI, but none have been validated for detecting subtle functional changes in clinically normal ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究
doi:10.2174/156720501205150526115003
更新日期:2015-01-01 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) and frontotemporal dementia (FTD) are the most common types of dementia in the presenile population. Episodic memory impairment, the clinical hallmark of AD, can also be encountered in patients with FTD, complicating accurate diagnosis. Several studies in FTD have correlated memory deficits wi...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011310030013
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called "amyloid cascade hypothesis" has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflamm...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205014666170505094549
更新日期:2018-02-22 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:BACKGROUND:The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. METHODS AND FINDINGS:AD patients aged 50-85 years were ra...
journal_title:Current Alzheimer research
pub_type: 杂志文章,随机对照试验
doi:10.2174/156720509787313961
更新日期:2009-02-01 00:00:00
abstract::In the last decade, several radiolabeled compounds have been developed for the imaging in vivo of amyloid pathology by means of Positron Emission Tomography (PET). Among these, 18F Florbetaben appear to be one of the most reliable for its high affinity for amyloid plaques in brain and its radio-chemical properties tha...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160620114309
更新日期:2017-01-01 00:00:00
abstract::The serine hydrolase butyrylcholinesterase (BChE), like the related enzyme acetylcholinesterase (AChE), co-regulates metabolism of the neurotransmitter acetylcholine. In the human brain BChE is mainly expressed in white matter and glia and in distinct populations of neurons in regions that are important in cognition a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160404120542
更新日期:2016-01-01 00:00:00
abstract::The increasing prevalence of obesity world-wide has an expected consequent increase in diabetes and cardiovascular disease. Less attention has been paid to the effect of obesity on dementia. This overview discusses methodological issues related to the epidemiologic study of obesity and dementia, reviews results of lon...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362074
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:In recent years, 5-hydroxytryptamine subtype 6 receptor (5-HT6 receptor, 5- HT6R) has emerged as a promising therapeutic target for the treatment of neuropathological disorders, including Alzheimer's disease (AD) and schizophrenia. 5-HT6 receptors were hypothesized to be implicated in the processes of learni...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666161108105005
更新日期:2017-01-01 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::Cholesterol-induced production of amyloid beta (Abeta) as a putative neurotoxin in Alzheimer's disease (AD), along with epidemiological evidence, suggests that statin drugs may provide benefit in treatment of the disorder. We tested the effect of once daily atorvastatin calcium (80 mg; two 40 mg tablets) on cognitive ...
journal_title:Current Alzheimer research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2174/1567205054367900
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:Impairment in instrumental activities of daily living (IADL) starts as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. However, most IADL scales have not shown IADL alterations in clinically normal (CN) elderly. The objective of this study was to det...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666141001120903
更新日期:2014-01-01 00:00:00
abstract::Evidence from basic molecular biology has noted a critical role of GSK-3 in Alzheimer's disease (AD) pathogenesis such as beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangle (NFT), and neuronal degeneration. Aβ generation and deposition represents a key feature and is generated from ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720512802455386
更新日期:2012-09-01 00:00:00
abstract::Alzheimer's disease (AD) is one of the most common causes of dementia. Despite several decades of research in AD, there is no standard disease- modifying therapy available and currentlyapproved drugs provide only symptomatic relief. Stem cells hold immense potential to regenerate damaged tissues and are currently test...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160314145347
更新日期:2017-01-01 00:00:00
abstract::Alzheimer's disease (AD) is currently the most prominent form of dementia among the elderly. Although AD manifests in late adult life, it is not clear when the disease actually starts and how long the neuropathological processes take to develop AD. The major unresolved question is the timing and the nature of triggeri...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362164
更新日期:2007-04-01 00:00:00
abstract::At present, the etiology of Alzheimer's disease (AD) is still unclear, but both genetic and non-genetic factors are thought to take part in the etiopathogenesis of AD. Epidemiologic researches revealed that genetic factors played a decisive role in the development of both early-onset AD (EOAD) and late-onset AD (LOAD)...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/15672050113109990155
更新日期:2013-10-01 00:00:00
abstract::High levels of cholesterol have been proposed as a risk factor for Alzheimer's disease (AD). Polymorphism of genes encoding proteins that regulate cholesterol metabolism have also been associated with the frequency of Alzheimer's development. Some studies have shown that cholesterol-lowering drugs reduce the frequency...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510791050821
更新日期:2010-05-01 00:00:00
abstract::With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in communi...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720501108140910123112
更新日期:2014-01-01 00:00:00
abstract:INTRODUCTION:Histaminergic H3 receptors may play a role in modulating cholinergic and monoaminergic neurotransmission. This Phase II study evaluated the efficacy and safety of GSK239512, a highly potent, brain penetrant H3 receptor antagonist as monotherapy treatment for subjects with mild-to-moderate probable Alzheime...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/1567205010666131212110148
更新日期:2014-01-01 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::Changes in rRNA and rDNA expression have been associated with cellular and organism aging and have been linked to Alzheimer's disease (AD) pathogenesis. In this study, we investigated the mRNA expression of ribosomal genes (28S/18S) and β-amyloid precursor protein (APP) in different post mortem brain tissue regions (t...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666151027124017
更新日期:2015-01-01 00:00:00