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 coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. METHODS:In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. RESULTS:In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. CONCLUSION:In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

journal_name

Curr Alzheimer Res

authors

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

doi

10.2174/1567205016666190816130516

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

723-731

issue

8

eissn

1567-2050

issn

1875-5828

pii

CAR-EPUB-100279

journal_volume

16

pub_type

杂志文章
  • Intracellular accumulation of toxic turn amyloid-β is associated with endoplasmic reticulum stress in Alzheimer's disease.

    abstract::Amyloid-β protein (Aβ) accumulates in the neurons of Alzheimer's disease (AD) patients at an early stage of the disease. Recently, we found that Aβ with a toxic turn at positions 22 and 23 accumulates in neurons in AD brain. Here, we studied the accumulation of Aβ, toxic turn Aβ and high-molecular-weight Aβ oligomers ...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章

    doi:

    authors: Soejima N,Ohyagi Y,Nakamura N,Himeno E,Iinuma KM,Sakae N,Yamasaki R,Tabira T,Murakami K,Irie K,Kinoshita N,LaFerla FM,Kiyohara Y,Iwaki T,Kira J

    更新日期:2013-01-01 00:00:00

  • Alzheimer's disease and intelligence.

    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

    authors: Yeo RA,Arden R,Jung RE

    更新日期:2011-06-01 00:00:00

  • Acetylcholinesterase Inhibitor Donepezil Effects on Plasma β-Hydroxybutyrate Levels in the Treatment of Alzheimer's Disease.

    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

    authors: Wan L,Lu J,Fu J,Huang J,Yang Q,Xin B,Chen L,Huo Y,Zhong Y,Guo C

    更新日期:2018-01-01 00:00:00

  • Autoimmunity in Alzheimer's disease as evidenced by plasma immunoreactivity against RAGE and Abeta42: complication of diabetes.

    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

    authors: Mruthinti S,Schade RF,Harrell DU,Gulati NK,Swamy-Mruthinti S,Lee GP,Buccafusco JJ

    更新日期:2006-07-01 00:00:00

  • Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline.

    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

    authors: Yurko-Mauro K

    更新日期:2010-05-01 00:00:00

  • Regulatory chaperone complexes in neurodegenerative diseases: a perspective on therapeutic intervention.

    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

    authors: Carman A,Kishinevsky S,Koren J 3rd,Luo W,Chiosis G

    更新日期:2014-01-01 00:00:00

  • Lead (Pb) in Alzheimer's Dementia: A Systematic Review of Human Case- Control Studies.

    abstract:BACKGROUND:Alzheimer's Dementia (AD) has a complex pathophysiology that is incompletely understood. Chronic, low-level environmental lead (Pb) exposure is associated with cognitive impairment, hypertension and mortality, and has been proposed as a potential cause of AD. OBJECTIVE:We aimed to review the literature to c...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章

    doi:10.2174/1567205016666190311101445

    authors: Brown EE,Shah P,Pollock BG,Gerretsen P,Graff-Guerrero A

    更新日期:2019-01-01 00:00:00

  • 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 compo...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章,评审

    doi:10.2174/1567205043480528

    authors: Uemura K,Kuzuya A,Shimohama S

    更新日期:2004-02-01 00:00:00

  • Alzheimer's Disease and NQO1: Is there a Link?

    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

    authors: Chhetri J,King AE,Gueven N

    更新日期:2018-01-01 00:00:00

  • Atorvastatin therapy lowers circulating cholesterol but not free radical activity in advance of identifiable clinical benefit in the treatment of mild-to-moderate AD.

    abstract::Cholesterol-induced production of amyloid beta (Abeta) as a putative neurotoxin in Alzheimer's disease (AD), along with epidemiological evidence, suggests that statin drugs may provide benefit in treatment of the disorder. We tested the effect of once daily atorvastatin calcium (80 mg; two 40 mg tablets) on cognitive ...

    journal_title:Current Alzheimer research

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2174/1567205054367900

    authors: Sparks DL,Sabbagh MN,Connor DJ,Lopez J,Launer LJ,Petanceska S,Browne P,Wassar D,Johnson-Traver S,Lochhead J,Ziolkowski C

    更新日期:2005-07-01 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

  • Altered functional connectivity of the marginal division in Alzheimer's disease.

    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

    authors: Zhang Z,Liu Y,Zhou B,Zheng J,Yao H,An N,Wang P,Guo Y,Dai H,Wang L,Shu S,Zhang X,Jiang T

    更新日期:2014-02-01 00:00:00

  • FTD and ALS: a tale of two diseases.

    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

    authors: Ferrari R,Kapogiannis D,Huey ED,Momeni P

    更新日期:2011-05-01 00:00:00

  • The role of α-synuclein in neurodegenerative diseases: from molecular pathways in disease to therapeutic approaches.

    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

    authors: Al-Mansoori KM,Hasan MY,Al-Hayani A,El-Agnaf OM

    更新日期:2013-07-01 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

  • Gamma-secretase inhibition and modulation for Alzheimer's disease.

    abstract::Gamma-secretase is a multi-protein complex that proteolyzes the transmembrane region of the amyloid beta-peptide (Abeta) precursor (APP), producing the Abeta peptide implicated in the pathogenesis of Alzheimer's disease (AD). This protease has been a top target for AD, and various inhibitors have been identified, incl...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章,评审

    doi:10.2174/156720508783954767

    authors: Wolfe MS

    更新日期:2008-04-01 00:00:00

  • TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders: new drug candidates and targets.

    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

    authors: Tweedie D,Sambamurti K,Greig NH

    更新日期:2007-09-01 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

  • Therapeutic approaches to modulating glutathione levels as a pharmacological strategy in Alzheimer's disease.

    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

    authors: Peter C,Braidy N,Zarka M,Welch J,Bridge W

    更新日期:2015-01-01 00:00:00

  • The Test Your Memory (TYM) Test Outperforms the MMSE in the Detection of MCI and Dementia.

    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

    authors: van de Zande E,van de Nes JC,Jansen I,van den Berg MN,Zwart AF,Bimmel D,Rijkers GT,Andringa G

    更新日期:2017-01-01 00:00:00

  • Neurotrophins: from pathophysiology to treatment in Alzheimer's disease.

    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

    authors: Schulte-Herbrüggen O,Jockers-Scherübl MC,Hellweg R

    更新日期:2008-02-01 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

  • Memory and consciousness in Alzheimer's disease.

    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

    authors: Souchay C,Moulin CJ

    更新日期:2009-06-01 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

  • Targeting PPARalpha in Alzheimer's Disease.

    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

    authors: D'Orio B,Fracassi A,Ceru MP,Moreno S

    更新日期:2018-02-22 00:00:00

  • VEGF, a mediator of the effect of experience on hippocampal neurogenesis.

    abstract::Rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show an increase in hippocampal neurogenesis. We show that both environmental enrichment, as well as performance in the Morris water maze, a hippocampal-dependent learning task, leads to an increase in local VEGF expres...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章,评审

    doi:10.2174/156720506775697133

    authors: During MJ,Cao L

    更新日期:2006-02-01 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

  • 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

  • AVN-322 is a Safe Orally Bio-Available Potent and Highly Selective Antagonist of 5-HT6R with Demonstrated Ability to Improve Impaired Memory in Animal Models.

    abstract:BACKGROUND:In recent years, 5-hydroxytryptamine subtype 6 receptor (5-HT6 receptor, 5- HT6R) has emerged as a promising therapeutic target for the treatment of neuropathological disorders, including Alzheimer's disease (AD) and schizophrenia. 5-HT6 receptors were hypothesized to be implicated in the processes of learni...

    journal_title:Current Alzheimer research

    pub_type: 杂志文章

    doi:10.2174/1567205013666161108105005

    authors: Ivachtchenko AV,Ivanenkov YA,Veselov MS,Okun IM

    更新日期:2017-01-01 00:00:00

  • Identification of human ABAD inhibitors for rescuing Aβ-mediated mitochondrial dysfunction.

    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

    authors: Valaasani KR,Sun Q,Hu G,Li J,Du F,Guo Y,Carlson EA,Gan X,Yan SS

    更新日期:2014-02-01 00:00:00