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 levels as a therapeutic target to treat these conditions include the administration of GSH itself, and low toxicity forms of the limiting amino acid for GSH synthesis; cysteine. However, passive GSH uptake is limited due to an unfavourable concentration gradient between the plasma and cytosol. Similarly, cysteine prodrugs have demonstrated limited efficacy to elevate depleted GSH levels in several in vivo and in vitro models of disease. It has been suggested that the decline in GSH levels in AD, may be associated with down regulation of GSH homeostasis rather than substrate limitation. Cellular GSH homeostasis is regulated by non-allosteric feedback inhibition exerted by GSH on glutamate cysteine ligase (GCL), which is responsible for the synthesis of the GSH precursor γ-glutamylcysteine (GGC). In conditions involving down regulated GSH homeostasis, GGC serves as a crucialrate-limiting substrate for GSH synthetase, the main enzyme responsible for condensing glycine with GGC to form the final thiol tripeptide, GSH. In this review, we focus on the therapeutic potential of GGC to elevate cellular GSH levels. We also discuss the efficacy of GGC prodrugs which would be taken up and converted by the unregulated GS to GSH, and the administration of modified GSH compounds, such as GSH esters that could potentially overcome the concentration gradient that prohibits passive GSH uptake, in AD.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Peter C,Braidy N,Zarka M,Welch J,Bridge Wdoi
10.2174/1567205012666150302160308subject
Has Abstractpub_date
2015-01-01 00:00:00pages
298-313issue
4eissn
1567-2050issn
1875-5828pii
CAR-EPUB-65580journal_volume
12pub_type
杂志文章,评审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::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 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::Alzheimer's disease (AD) is a neurodegenerative disorder linked to protein misfolding and aggregation. AD is pathologically characterized by senile plaques formed by extracellular Amyloid-β (Aβ) peptide and Intracellular Neurofibrillary Tangles (NFT) formed by hyperphosphorylated tau protein. Extensive synaptic loss a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205016666190321163438
更新日期:2019-01-01 00:00:00
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 n...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666181212155147
更新日期:2019-01-01 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::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::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::Mutations in presenilin 1 (PS1) cause early-onset familial Alzheimer;s disease (FAD). Although FAD accounts for less than 5% of all cases of Alzheimer;s disease (AD), extensive analyses of PS1 function have elucidated an important neuronal mechanism underling AD pathogenesis. PS1 is considered to be an essential compo...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205043480528
更新日期:2004-02-01 00:00:00
abstract::Anesthesia and surgery have been reported to produce long-term cognitive problems, and to accelerate neurodegenerative disorders in the elderly. In previous work, we found that inhaled anesthetics enhance fibril formation and cytotoxicity of amyloid beta peptide. In this work we show that the inhaled anesthetics halot...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720507781077278
更新日期:2007-07-01 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:OBJECTIVES:Memory evaluation is a key component in the accurate diagnosis of cognitive disorders.One memory procedure that has shown promise in discriminating disease-related cognitive decline from normal cognitive aging is the New York University Paragraph Recall Test; however, the effects of education have been unexa...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/15672050113109990140
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:The design of new heterodimeric dual binding site acetylcholinesterase inhibitors constitutes the main goal-directed to the development of new anticholinesterase agents with the expanded pharmacological profile. Multi-target compounds are usually designed by combining in a hybrid molecule with two or more ph...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180711110750
更新日期:2018-01-01 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::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::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::Today, the most reliable diagnosis for Alzheimer's disease (AD) is the post mortem identification of amyloid plaques, consisting of the Amyloid-beta (Abeta) peptide, (and neurofibrillary tangles) in the brain of the patient. Great efforts are being made to identify reliable biomarkers for AD that are suitable for mini...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509788486536
更新日期:2009-06-01 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:BACKGROUND:Curcumin has been of interest in the field of Alzheimer's disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666190816130516
更新日期:2019-01-01 00:00:00
abstract::Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneratio...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205012666150921095505
更新日期:2016-01-01 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::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:OBJECTIVE:Centrifuges are the principal means of generating physiological hypergravity and have been used for many medical purposes, including the therapy of psychiatric diseases and evaluation of vestibular system in the pilots. In particular, modern centrifuges have evolved into mechanically sophisticated precision i...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205015666171229225501
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::Pathological remodelling of astroglia represents an important component of the pathogenesis of Alzheimer's disease (AD). In AD astrocytes undergo both atrophy and reactivity; which may be specific for different stages of the disease evolution. Astroglial reactivity represents the generic defensive mechanism, and inhib...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666151116130104
更新日期:2016-01-01 00:00:00
abstract::From a clinical as well as a neuropathological point of view Alzheimer's disease (AD) has been the focus of intense research for more than three decades. Most studies to identify morphometric correlates with the declining cognitive function in normal aging and AD have employed semi-quantitative methods to assess neuro...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720505774330528
更新日期:2005-10-01 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::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::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::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