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. These species, called chaperone client proteins, include the pathogenic factors of numerous neurodegenerative disorders, including tau in Alzheimer's disease, α-synuclein and LRRK2 in Parkinson's disease, SOD-1, TDP-43 and FUS in amyotrophic lateral sclerosis, and polyQ-expanded proteins such as huntingtin in Huntington's disease. In depth study of two molecular chaperones, Hsp90 and Hsc70, has led to a greater understanding of aberrant client fate and how retarding the chaperone system can promote clearance of these pathogenic clients. Here we discuss how chaperone interactions and small molecule inhibitors can regulate the burden of aberrant client signaling in these neurological disorders.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Carman A,Kishinevsky S,Koren J 3rd,Luo W,Chiosis Gdoi
10.2174/1567205010666131119233044subject
Has Abstractpub_date
2014-01-01 00:00:00pages
59-68issue
1eissn
1567-2050issn
1875-5828pii
CAR-EPUB-57540journal_volume
11pub_type
杂志文章,收录出版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:Accumulating evidence suggests that multi-target directed ligands have great potential for the treatment of complex diseases such as Alzheimer's Disease (AD). OBJECTIVE:To evaluate novel chimeric 8-hydroxyquinoline ligands with merged pharmacophores as potential multifunctional ligands for AD. METHODS:Nitr...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666191010130351
更新日期:2019-01-01 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::In this review, the basic mechanism of the parasympathetic nervous effect on the heart is discussed. This is expanded to clinical situations to clarify what can happen to patients after cholinesterase (ChE) inhibitor is administered and to avoid unnecessary adverse effects. The parasympathetic nervous system can affec...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205043332009
更新日期:2004-11-01 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:BACKGROUND:The lack of diagnostic tools and disease-modifying treatments against Alzheimer's disease (AD) and related disorders, collectively known as tauopathies, has led to a socioeconomic burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome changes that could help us understand...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180813152043
更新日期:2018-01-01 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: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::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
abstract::Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer’s disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecul...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795563746
更新日期:2011-05-01 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: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::Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer's disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids t...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205015666180911151716
更新日期:2018-01-01 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::Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO S...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666141107125104
更新日期:2014-01-01 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::To search for potential mechanism that might alter synaptic transmission following Abeta increase we have examined the presynaptic component of transmitter release. As parameters of synaptic transmission that might underlie presynaptic mechanisms, we have used paired-pulse facilitation (PPF), post-tetanic potentiation...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205053585936
更新日期:2005-04-01 00:00:00
abstract::A crucial need exists for reliable Alzheimer's disease (AD) diagnostic and prognostic tests. Given its intimate communication with the brain, the cerebrospinal fluid (CSF) has been surveyed intensively for reliable AD biomarkers. The heterogeneity of AD pathology and the unavoidable difficulties associated with the cl...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720509788929318
更新日期:2009-08-01 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:BACKGROUND:Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients. Ocular imaging of biomarkers, such as drusen in the peripheral retina, could provide an alternative method to diagnose AD. OBJECTIVE:This s...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180123122637
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:ACTION, a 24-week, prospective, randomized, parallel-group, double-blind study in patients with severe Alzheimer's disease (AD), demonstrated significant efficacy of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch on the Severe Impairment Battery (SIB) and Alzheimer's Disease Cooperative Study-Activities ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/1567205011666141218122835
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:It is well known that alterations in astrocytes occur in Alzheimer's disease and reactive astrogliosis is one of the hallmarks of the disease. Recently, data has emerged that suggests that alterations in astrocytes may also occur early in the pathogenesis of the disease. OBJECTIVE:The aim of present work wa...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180613113924
更新日期:2018-01-01 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::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) accumulatio...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/15672050113109990132
更新日期:2013-07-01 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::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::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: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::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:Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer's Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205016666191023114015
更新日期:2019-01-01 00:00:00