Abstract:
BACKGROUND:Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer's disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is used to identify new and safer 'disease-modifying drugs'. METHODS:Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism. Further, the potential of the predicted molecules to inhibit acetylcholinesterase (AChE) activity and their ability to protect neurons from degeneration was determined through in-vitro assays. RESULTS:Based on in-silico AChE interaction studies, we predicted quercetin, caffeine, ascorbic acid and gallic acid to be potential AChE inhibitors. We confirmed the AChE inhibitory potential of these molecules through in-vitro AChE inhibition assay and compared results with donepezil and begacestat. Herbal molecules significantly inhibited enzyme activity and inhibition for quercetin and caffeine did not show any significant difference from donepezil. Further, the tested molecules did not show any neurotoxicity against primary (E18) hippocampal neurons. We observed that quercetin and caffeine significantly improved neuronal survival and efficiently protected hippocampal neurons from HgCl2 induced neurodegeneration, which other molecules, including donepezil and begacestat, failed to do. CONCLUSION:Quercetin and caffeine have the potential as "disease-modifying drugs" and may find application in the management of neurological disorders such as AD.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Kumar A,Mehta V,Raj U,Varadwaj PK,Udayabanu M,Yennamalli RM,Singh TRdoi
10.2174/1567205016666181212155147subject
Has Abstractpub_date
2019-01-01 00:00:00pages
116-127issue
2eissn
1567-2050issn
1875-5828pii
CAR-EPUB-95205journal_volume
16pub_type
杂志文章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: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
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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::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::Elevated amyloid-beta peptide (Abeta) and loss of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery of an Abeta - nAChR interaction, much effort has been expended to characterize the consequences of high versus low concentrations of Abeta on n...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510790274464
更新日期:2010-02-01 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
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::Metabotropic glutamate receptor 5 (mGluR5) is highly expressed throughout the forebrain and hippocampus. Several lines of evidence support the role of this receptor in brain development and developmental disorders, as well as in neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the expre...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140812115423
更新日期:2014-01-01 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:OBJECTIVE:To carry out meaningful comparisons on results of different research studies on mild cognitive impairment (MCI), it is critical to select an appropriate objective memory test to examine memory deficit. We aim to refine the operational criteria of amnestic MCI (aMCI) on neuropsychological tests that optimally ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150530202729
更新日期:2015-01-01 00:00:00
abstract::A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, suc...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720511795745276
更新日期:2011-06-01 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::Mild cognitive impairment (MCI) is a nosological entity associated with a higher risk of developing dementia. Previous evidence indicates that behavioral and psychological symptoms of dementia (BPSDs) frequently occur in individuals of MCI. These neuropsychiatric manifestations may predict conversion to dementia. Howe...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160502123129
更新日期:2016-01-01 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::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::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: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::Serum levels of β-amyloid (Aβ) peptides may represent an early biomarker in the diagnosis of Alzheimer's disease (AD). In the present study, we investigated the temporal kinetic changes in the levels of serum Aβ 1-42 and 40 in an amyloid precursor protein (APP)/presenilin (PS)1 double transgenic mouse model of AD. Ser...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/15672050113106660159
更新日期:2013-11-01 00:00:00
abstract::Lipids have many important yet distinct functions in cellular homeostasis such as forming an impermeable barrier separating intracellular and extracellular compartments, providing a matrix for the appropriate interactions of membrane-associated proteins, and serving as storage reservoirs for biologically active second...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205052772786
更新日期:2005-01-01 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:BACKGROUND:Vascular disease is associated with increased risk of dementia. Vascular health worsens with age. We investigated the relationship between self-reported vascular disease and brain pathology. METHODS:Brain donations to the population-based MRC Cognitive Function and Ageing Study (n=456, age range 66-103 year...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512801322654
更新日期:2012-07-01 00:00:00
abstract::Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease (AD). The formation of the cytoplasmic inclusions named "Lewy bodies" in the brain, considered to be a marker for neuronal degeneration in PD and dementia with Lewy bodies. However, Lewy bodies (LBs) are also obser...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205011310060002
更新日期:2013-07-01 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::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: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::The aetiology of major neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is still unknown, but increasing evidences suggest that glutamate and mitochondria are two prominent players in the oxidative stress (OS) process that underlie these illnesses. Although AD and PD have distin...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666151218132725
更新日期:2016-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common diagnosis among dementia. As increasing longevity results in larger numbers of AD patients and thus rising economic costs, there has been intense research about the pathophysiology and treatment strategies during the last years. Since neurotrophic factors are not only respon...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720508783884620
更新日期:2008-02-01 00:00:00
abstract::The remarkable potentiality of bone marrow-derived mesenchymal stem cells (BM-MSCs) after transplantation to models of neurological disease and injury has been described. We have previously published data confirming the influence of BM-MSCs on β-amyloid (Aβ) deposition in an Alzheimer's disease (AD) mouse model. Howev...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disease characterised by a progressive decline in cognitive function and represents a major healthcare challenge worldwide. Increasing evidence indicates that mitochondrial dysfunction mediated oxidative stress plays a significant role in the pathophysiological...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205014666170203095802
更新日期:2018-01-01 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