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 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; cysteineHowever, passive GSH uptake is limited due to an unfavourable concentration gradient between the plasma and cytosol. Similarly, cysteine prodrugs have demonstrated limited efficacyto elevatedepleted GSH levels in several in vivo and in vitro models of disease.It has beensuggestedthat the decline in GSH levels in AD, may be associated with down regulation ofGSH homeostasis rather than substrate limitation. Cellular GSH homeostasis is regulatedby 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 asa 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,andthe 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
Braidy N,Zarka M,Welch J,Bridge Wsubject
Has Abstractpub_date
2015-03-24 00:00:00eissn
1567-2050issn
1875-5828pii
CAR-EPUB-66149pub_type
杂志文章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::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::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::Apoptosis has been postulated to play a possible causal role in the onset of Alzheimer's disease due to shortage of trophic supply, deafferentation and excessive production of free radicals. Many experiments in the past have demonstrated the requirement of de novo gene expression during neuronal apoptosis. In view of ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506778249416
更新日期:2006-09-01 00:00:00
abstract::Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. A characteristic of AD is the accumulation of plaques in the brain of AD patients, and theses plaques mainly consist of aggregates of amyloid beta-peptide (Abeta). All converging lines of evidence sugg...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720508784533321
更新日期:2008-06-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. T...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205011666140618103827
更新日期:2014-01-01 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::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: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::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::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::To compare differences in evolutionary progressions from Mild Cognitive Impairment (MCI) to dementia of Alzheimer's type (DAT) or to vascular dementia (VaD) versus normal aging, subjects identified as MCI or as cognitively normal (CN) during standard cognitive evaluations among a large epidemiological study designed t...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720505774932223
更新日期:2005-12-01 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 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 t...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512802455322
更新日期:2012-09-01 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::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::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::When Alzheimer's disease (AD) progresses, several pathological features arise including accumulation of misfolded protein aggregates [e.g., amyloid-β (Aβ) plaques], metal ion dyshomeostasis, and oxidative stress. These characteristics are recently suggested to be interconnected through a potential factor, metal-associ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150504150125
更新日期:2015-01-01 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::According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160222112444
更新日期:2016-01-01 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::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::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::Memory loss is a prominent health concern, second only to heart disease for older individuals. Docosahexaenoic acid (DHA), the principle omega-3 fatty acid in brain and heart, plays an important role in neural and cardiac function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly and Al...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510791050911
更新日期:2010-05-01 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: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::Acetylcholinesterase (AChE) plays a crucial physiological role in termination of impulse transmission at cholinergic synapses through rapid hydrolysis of acetylcholine. In addition, it was implicated in amyloid plaque formation, a hallmark of Alzheimer's disease (AD), and most of the drugs used in AD treatment are ACh...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205053585909
更新日期:2005-04-01 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::What are the resources needed by clinical pharmacology to test drugs in ways that model how the practitioner achieves optimal effectiveness and safety with each patient? I describe the applications of test-retest standard error of measurement, clinical decision rules, means or other statistical summaries of observatio...
journal_title:Current Alzheimer research
pub_type: 历史文章,杂志文章,评审
doi:10.2174/156720507781788828
更新日期:2007-09-01 00:00:00