Protein trafficking and Alzheimer's disease.

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 component of gamma-secretase, which cleaves amyloid precursor protein (APP) at the transmembrane region and releases amyloid beta (Abeta) peptide. In addition to this well-documented function, a growing amount of evidence suggests that PS1 is involved in the intracellular trafficking of selected membrane proteins (i.e. APP, nicastrin, trkB, telencephalin). Recently, we have also shown that PS1 is involved in the trafficking of N-cadherin from the endoplasmic reticulum to the plasma membrane via the microtubule network. N-cadherin is localized at the synaptic junctional complex, providing an adhesive force across the synaptic cleft, and the its regulation is crucial for the neuron to exert its specific function, i.e. synaptic activity. In a mature neuron, polarized targeting of proteins from the cell body to the axonal and dendritic processes is essential for its proper function, especially, for the maintenance of synaptic function. Alterations in protein transport caused by a dysfunction in PS1 could lead to a disturbance in synaptic transmission and finally to neurodegeneration. This article will review the current knowledge of PS1 function in protein trafficking and discuss its potential role in AD pathogenesis.

journal_name

Curr Alzheimer Res

authors

Uemura K,Kuzuya A,Shimohama S

doi

10.2174/1567205043480528

keywords:

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

1-10

issue

1

eissn

1567-2050

issn

1875-5828

journal_volume

1

pub_type

杂志文章,评审
  • Computer based classification of MR scans in first time applicant Alzheimer patients.

    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

    authors: Polat F,Demirel SO,Kitis O,Simsek F,Haznedaroglu DI,Coburn K,Kumral E,Gonul AS

    更新日期:2012-09-01 00:00:00

  • Therapeutic Strategies Targeting Amyloid-β in Alzheimer's Disease.

    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

    authors: Pinheiro L,Faustino C

    更新日期:2019-01-01 00:00:00

  • Perispinal etanercept for treatment of Alzheimer's disease.

    abstract:BACKGROUND:Increasing basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of Alzheimer's Disease. Excess TNF-alpha, a cytokine with pleotropic effects in the CNS, has been suggested to be involved in the pathogenesis of AD. In addition to its pro-infl...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章,评审

    doi:10.2174/156720507783018217

    authors: Tobinick E

    更新日期:2007-12-01 00:00:00

  • Auditory Verbal Learning Test is Superior to Rey-Osterrieth Complex Figure Memory for Predicting Mild Cognitive Impairment to Alzheimer's Disease.

    abstract:OBJECTIVE:To carry out meaningful comparisons on results of different research studies on mild cognitive impairment (MCI), it is critical to select an appropriate objective memory test to examine memory deficit. We aim to refine the operational criteria of amnestic MCI (aMCI) on neuropsychological tests that optimally ...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章

    doi:10.2174/1567205012666150530202729

    authors: Zhao Q,Guo Q,Liang X,Chen M,Zhou Y,Ding D,Hong Z

    更新日期:2015-01-01 00:00:00

  • Epidemiology and etiology of Alzheimer's disease: from genetic to non-genetic factors.

    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

    authors: Jiang T,Yu JT,Tian Y,Tan L

    更新日期:2013-10-01 00:00:00

  • Metabotropic glutamate receptor 5 in Down's syndrome hippocampus during development: increased expression in astrocytes.

    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

    authors: Iyer AM,van Scheppingen J,Milenkovic I,Anink JJ,Lim D,Genazzani AA,Adle-Biassette H,Kovacs GG,Aronica E

    更新日期:2014-01-01 00:00:00

  • High Contrast and Resolution Labeling of Amyloid Plaques in Tissue Sections from APP-PS1 Mice and Humans with Alzheimer's Disease with the Zinc Chelator HQ-O: Practical and Theoretical Considerations.

    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

    authors: Schmued L,Raymick J,Sarkar S

    更新日期:2019-01-01 00:00:00

  • Amyloid β oligomers decrease hippocampal spontaneous network activity in an age-dependent manner.

    abstract::Soluble amyloid beta (Abeta) oligomers might trigger early cognitive impairment in Alzheimer's Disease (AD) through the impairment of proper neuronal network function. We have recently shown that the short sequence Abeta(25-35) affects the spontaneous activity in hippocampal slices, when was added to the bath, at high...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章

    doi:10.2174/156720510791383859

    authors: Balleza-Tapia H,Huanosta-Gutiérrez A,Márquez-Ramos A,Arias N,Peña F

    更新日期:2010-08-01 00:00:00

  • Quality of education and memory test performance in older men: the New York University Paragraph Recall Test normative data.

    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

    authors: Mathews M,Abner E,Caban-Holt A,Dennis BC,Kryscio R,Schmitt F

    更新日期:2013-09-01 00:00:00

  • How and when environmental agents and dietary factors affect the course of Alzheimer's disease: the "LEARn" model (latent early-life associated regulation) may explain the triggering of AD.

    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

    authors: Lahiri DK,Maloney B,Basha MR,Ge YW,Zawia NH

    更新日期:2007-04-01 00:00:00

  • Alzheimer's Disease and Retinal Degeneration: A Glimpse at Essential Trace Metals in Ocular Fluids and Tissues.

    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

    authors: Micera A,Bruno L,Cacciamani A,Rongioletti M,Squitti R

    更新日期:2019-01-01 00:00:00

  • A Multicentre Italian Validation Study in Aging Adults with Down Syndrome and Other Forms of Intellectual Disabilities: Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.

    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

    authors: Gomiero T,Bertelli M,Deb S,Weger E,Marangoni A,De Bastiani E,Mantesso U,De Vreese LP

    更新日期:2017-01-01 00:00:00

  • Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome.

    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

    authors: Hamlett ED,Boger HA,Ledreux A,Kelley CM,Mufson EJ,Falangola MF,Guilfoyle DN,Nixon RA,Patterson D,Duval N,Granholm AC

    更新日期:2016-01-01 00:00:00

  • Inhibitory Activity Of Curcumin Derivatives Towards Metal-free And Metal-induced Amyloid-β Aggregation.

    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

    authors: Kochi A,Lee HJ,Vithanarachchi SM,Padmini V,Allen MJ,Lim MH

    更新日期:2015-01-01 00:00:00

  • Tau aggregation is a therapeutic target for Alzheimer's disease.

    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

    authors: Takashima A

    更新日期:2010-12-01 00:00:00

  • Roles of glycogen synthase kinase 3 in Alzheimer's disease.

    abstract::Evidence from basic molecular biology has noted a critical role of GSK-3 in Alzheimer's disease (AD) pathogenesis such as beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangle (NFT), and neuronal degeneration. Aβ generation and deposition represents a key feature and is generated from ...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章,评审

    doi:10.2174/156720512802455386

    authors: Cai Z,Zhao Y,Zhao B

    更新日期:2012-09-01 00:00:00

  • Mitochondrial dysfunction and Alzheimer's disease.

    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

    authors: Chen X,Stern D,Yan SD

    更新日期:2006-12-01 00:00:00

  • Amyloid-β in the Cerebrospinal Fluid of APP Transgenic Mice Does not Show Prion-like Properties.

    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

    authors: Skachokova Z,Sprenger F,Breu K,Abramowski D,Clavaguera F,Hench J,Staufenbiel M,Tolnay M,Winkler DT

    更新日期:2015-01-01 00:00:00

  • Isotyping the human TOMM40 variable-length polymorphism by gene amplification and restriction digest.

    abstract::Recent studies have shown that the translocase of outer mitochondrial membrane 40 homolog (TOMM40) contains a polymorphic poly-T variant, the long variant of which is associated with an increase in AD incidence among APOE 3 carriers. Current methods to isotype the poly-T region rely on long PCR, subcloning and sequenc...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章

    doi:10.2174/156720512804142921

    authors: Greco SJ,Hamzelou A,Johnston JM,Richardson S,Smith MA,Perry G,Ashford JW,Tezapsidis N

    更新日期:2012-12-01 00:00:00

  • Evaluating high-dose rivastigmine patch in severe Alzheimer's disease: analyses with concomitant memantine usage as a factor.

    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

    authors: Grossberg GT,Farlow MR,Meng X,Velting DM

    更新日期:2015-01-01 00:00:00

  • Default mode, executive function, and language functional connectivity networks are compromised in mild Alzheimer's disease.

    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

    authors: Weiler M,Fukuda A,Massabki LH,Lopes TM,Franco AR,Damasceno BP,Cendes F,Balthazar ML

    更新日期:2014-03-01 00:00:00

  • Cholesterol, lipids, amyloid Beta, and Alzheimer's.

    abstract::High levels of cholesterol have been proposed as a risk factor for Alzheimer's disease (AD). Polymorphism of genes encoding proteins that regulate cholesterol metabolism have also been associated with the frequency of Alzheimer's development. Some studies have shown that cholesterol-lowering drugs reduce the frequency...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章,评审

    doi:10.2174/156720510791050821

    authors: Vestergaard M,Hamada T,Morita M,Takagi M

    更新日期:2010-05-01 00:00:00

  • Drusen in the Peripheral Retina of the Alzheimer's Eye.

    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

    authors: Ukalovic K,Cao S,Lee S,Tang Q,Beg MF,Sarunic MV,Hsiung GR,Mackenzie IR,Hirsch-Reinshagen V,Cui JZ,Matsubara JA

    更新日期:2018-01-01 00:00:00

  • Analysis of genetic polymorphisms in acetylcholinesterase as reflected in different populations.

    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

    authors: Hasin Y,Avidan N,Bercovich D,Korczyn AD,Silman I,Beckmann JS,Sussman JL

    更新日期:2005-04-01 00:00:00

  • An Optimal Approach for Selecting Discriminant Regions for the Diagnosis of Alzheimer's Disease.

    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

    authors: Salas-Gonzalez D,Segovia F,Martínez-Murcia FJ,Lang EW,Gorriz JM,Ramırez J

    更新日期:2016-01-01 00:00:00

  • Structure-function implications in Alzheimer's disease: effect of Abeta oligomers at central synapses.

    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

    authors: Cerpa W,Dinamarca MC,Inestrosa NC

    更新日期:2008-06-01 00:00:00

  • The hyperforin derivative IDN5706 occludes spatial memory impairments and neuropathological changes in a double transgenic Alzheimer's mouse model.

    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

    authors: Cerpa W,Hancke JL,Morazzoni P,Bombardelli E,Riva A,Marin PP,Inestrosa NC

    更新日期:2010-03-01 00:00:00

  • Alzheimer's disease: spect and pet tracers for beta-amyloid imaging.

    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

    authors: Valotassiou V,Archimandritis S,Sifakis N,Papatriantafyllou J,Georgoulias P

    更新日期:2010-09-01 00:00:00

  • Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer's Disease Imaging.

    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

    authors: Sturzu A,Sheikh S,Kalbacher H,Nägele T,Weidenmaier C,Wegenast-Braun BM,Schilling N,Ernemann U,Heckl S

    更新日期:2019-01-01 00:00:00

  • Transcriptional Remodeling in Primary Hippocampal Astrocytes from an Alzheimer's Disease Mouse Model.

    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

    authors: Ruffinatti F,Tapella L,Gregnanin I,Stevano A,Chiorino G,Canonico PL,Distasi C,Genazzani AA,Lim D

    更新日期:2018-01-01 00:00:00