Abstract:
:Deterioration of the cortical cholinergic system is a leading neurochemical feature of Alzheimer's Disease (AD). This review summarizes evidence that the homomeric α7- nicotinic acetylcholine receptor (nAChR) plays a crucial role in the pathogenesis of this disease, which is characterized by amyloid-β (Aβ) accumulations and neurofibrillary tangles originating from of hyperphosphorylated tau protein. Aβ binds to α7-nAChRs with a high affinity, either activating or inhibiting this receptor in a concentration-dependent manner. There is strong evidence that α7-nAChRs are neuroprotective, reducing Aβ-induced toxicity; but co-localization of α7- nAChRs, Aβ and amyloid plaques also points to neurodegenerative actions. Aβ induces tau phosphorylation via α7-nAChR activation. Aβ influences hippocampus-dependent memory and long-term potentiation in a dose-dependent way: there is evidence that enhancement by picomolar Aβ concentrations is mediated by α7-nAChRs, whereas inhibition by nanomolar concentrations is independent of nAChRs and probably mediated by small Aβ42 oligomers. α7-nAChRs located on vascular smooth muscle cells and astrocytes are also involved in the pathogenesis of AD. Although these data strongly point to an important role of α7-nAChRs in the development of AD, dose-dependence of the effects, rapid desensitization of the receptor and dependence of the effects on Aβ aggregation (monomers, oligomers, fibrils) make it difficult to develop simple therapeutic strategies acting upon this receptor.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Oz M,Lorke DE,Yang KH,Petroianu Gdoi
10.2174/15672050113109990132subject
Has Abstractpub_date
2013-07-01 00:00:00pages
618-30issue
6eissn
1567-2050issn
1875-5828pii
CAR-EPUB-20130429-1journal_volume
10pub_type
杂志文章,评审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::Protein folding, protein degradation, and protein stability are regulated by the molecular chaperones. Under pathogenic conditions, aberrant proteins can be dysfunctional, unregulated, or pathogenically mutated. These aberrant proteins are triaged by the chaperone network for the maintenance of cellular homeostasis. T...
journal_title:Current Alzheimer research
pub_type: 杂志文章,收录出版
doi:10.2174/1567205010666131119233044
更新日期:2014-01-01 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::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::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::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::The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effe...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140505094808
更新日期:2014-01-01 00:00:00
abstract::Based on the amyloid hypothesis, studies for AD therapy have been mostly focused on removing β-amyloid. Recent results of amyloid immunotherapy raised the question whether β-amyloid is sufficient target for AD therapy. Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hall...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510793611600
更新日期:2010-12-01 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:BACKGROUND:There is a growing body of pre-clinical evidence suggesting that lithium (Li) may protect neurons from a range of neurotoxic insults, hence the term neuroprotective effects. Does Li have similar effects also in human subjects? METHODS:We reviewed the neuroimaging literature investigating the association bet...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160219112712
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaque and neurofibrillary tangles in the brain. Studies have shown that neurons are able to re-enter the cell cycle, but not enough to enable full replication. This leads to cell death and consequent neurodegener...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205014666170713160407
更新日期:2018-01-01 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::Alzheimer's disease (AD) is the most common type of dementia in the US and much of the world with rates increasing exponentially from age 65. Increases in life expectancy in the last century have resulted in a large number of people living to old ages and will result in a quadrupling of AD cases by the middle of the c...
journal_title:Current Alzheimer research
pub_type: 历史文章,杂志文章,评审
doi:10.2174/156720506779025233
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) is the most widely used cognitive outcome measure in AD trials. Although errors in administration and scoring have been suggested as factors masking accurate estimates and potential effects of treatments, there have been few formal exam...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795745357
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by a multi-factorial etiology that is not completely understood. Donepezil is a first-line acetylcholinesterase inhibitor used for the treatment of AD that has been found, in addition to its potent acetylcholinesterase inhibitory ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180601091818
更新日期:2018-01-01 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::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::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::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 repor...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140130150108
更新日期:2014-02-01 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::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) 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:OBJECTIVES:REM sleep behavior disorder (RBD), with its main clinical symptoms of nightmares with dream-enacting behavior, is considered as a possible precursor of neurodegenerative disease. Obstructive Sleep Apnea Syndrome (OSAS) is known to be capable of provoking RBD-like symptoms by apneic event related arousals. Th...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205014666170523094938
更新日期:2017-01-01 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::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::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/OBJECTIVES:Increasing evidence suggests the importance of neuroinflammation in the pathogenesis of Alzheimer's disease (AD), which is a complex neurodegenerative disorder. Complement activation occurs in the brain of patients with AD and seems to contribute to an important local inflammatory state. Increased...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666161013091934
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:OBJECTIVE:The aim of this study was to evaluate the diagnostic accuracy and clinical usability of a Dutch translation of the Test Your Memory (TYM) test in patients with mild cognitive impairment (MCI) and dementia as compared to the Mini-Mental State Examination (MMSE), in the setting of the memory clinic of a general...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666161201202520
更新日期:2017-01-01 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