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 molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not yet understood. We have employed transgenic Drosophila models and optical coherence tomography imaging technology to analyze cardiac function in live adult Drosophila. Silencing of Drosophila ortholog of presenilins (dPsn) led to significantly reduced heart rate and remarkably age-dependent increase in end-diastolic vertical dimensions. In contrast, overexpression of dPsn increased heart rate. Either overexpression or silencing of dPsn resulted in irregular heartbeat rhythms accompanied by cardiomyofibril defects and mitochondrial impairment. The calcium channel receptor activities in cardiac cells were quantitatively determined via real-time RT-PCR. Silencing of dPsn elevated dIP3R expression, and reduced dSERCA expression; overexprerssion of dPsn led to reduced dRyR expression. Moreover, overexpression of dPsn in wing disc resulted in loss of wing phenotype and reduced expression of wingless. Our data provide novel evidence that changes in presenilin level leads to cardiac dysfunction, owing to aberrant calcium channel receptor activities and disrupted Wnt signaling transduction, indicating a pathogenic role for presenilin mutations in DCM pathogenesis.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Li A,Zhou C,Moore J,Zhang P,Tsai TH,Lee HC,Romano DM,McKee ML,Schoenfeld DA,Serra MJ,Raygor K,Cantiello HF,Fujimoto JG,Tanzi REdoi
10.2174/156720511795563746subject
Has Abstractpub_date
2011-05-01 00:00:00pages
313-22issue
3eissn
1567-2050issn
1875-5828pii
BSP/CAR /0153journal_volume
8pub_type
杂志文章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::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::This article presents a new paradigm of Artificial Neural Networks (ANNs): the Auto-Contractive Maps (Auto-CM). The Auto-CM differ from the traditional ANNs under many viewpoints: the Auto-CM start their learning task without a random initialization of their weights, they meet their convergence criterion when all thei...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720508785908928
更新日期:2008-10-01 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::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::In this study, we aimed to classify MR images for recognizing Alzheimer Disease (AD) in a group of patients who were recently diagnosed by clinical history and neuropsychiatric exams by using non-biased machine-learning techniques. T1 weighted MRI scans of 31 patients with probable AD and 31 age- and gender-matched co...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512802455359
更新日期:2012-09-01 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::Alzheimer's disease (AD) is characterized by mental and cognitive problems, particularly with memory, language, visuospatial skills (VS), and executive functions (EF). Advances in the neuroimaging of AD have highlighted dysfunctions in functional connectivity networks (FCNs), especially in the memory related default m...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140131114716
更新日期:2014-03-01 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::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::Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligo...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/15672050113106660176
更新日期:2014-01-01 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::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: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::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
abstract::The marginal division (MrD) is a neostriatum subregion that links the limbic system and basal nucleus of Meynert; it is an important subcortical center that is involved in learning and memory. Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. AD clinically m...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140110112608
更新日期:2014-02-01 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::Alzheimer's disease (AD) is one of the most common causes of dementia. Despite several decades of research in AD, there is no standard disease- modifying therapy available and currentlyapproved drugs provide only symptomatic relief. Stem cells hold immense potential to regenerate damaged tissues and are currently test...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160314145347
更新日期:2017-01-01 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::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::Alzheimer's disease (AD) is a devastating chronic neurodegenerative disease with currently no available disease modifying treatment. In recent years, the peptide amyloid-beta has been proposed as the major pathogenic force in the development and progression of AD. Microglia, the resident immune and phagocytic cells of...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509790147179
更新日期:2009-12-01 00:00:00
abstract::Amyloid beta peptide (Abeta), 42-residue peptide and its variations, is known to form amyloid fibrils in Alzheimer's disease. Solid-state NMR study reveals a parallel beta-sheet structure in the Abeta fibrils. The atomic level structure of Abeta in aqueous environment, however, has not been determined, because of its ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720508786898424
更新日期:2008-12-01 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:Various methodologies have been employed for the localization of amyloid plaques in numerous studies on Alzheimer's disease. The majority of these stains are thought to label the plaques by virtue of their affinity for aggregated Aβ. However, plaques are known to contain numerous other components, including ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666190725155038
更新日期:2019-01-01 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::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::Early diagnosis of Alzheimer`s disease (AD) is currently difficult and involves a complex approach including clinical assessment, neuroimaging, and measurement of amyloid-β (Aβ) and tau levels in cerebrospinal fluid (CSF). A better mechanistic understanding is needed to develop more accurate and even presymptomatic di...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150710115022
更新日期:2015-01-01 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: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: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