Curcumin labels amyloid pathology <i>in vivo</i>, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model

García-Alloza, Mónica; Borrelli, Laura A.; Rozkalne, Anete; Hyman, Bradley T.; Bacskai, Brian J.

doi:10.1111/j.1471-4159.2007.04613.x

Cited by 614 publications

(443 citation statements)

References 45 publications

(76 reference statements)

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“…Anti-ROS agents, including curcumin and phenyl-N-tert-butyl nitrene, reduce parenchymal amyloid burden in aged APP mice (60)(61)(62)(63). Other anti-ROS agents, however, are not effective (20,36,64).…”

Section: Discussionmentioning

confidence: 99%

“…Only three of the aforementioned pharmacologic studies and one of aforementioned genetic studies assessed the influence of ROS on CAA formation. Results from the pharmacological studies are as follows: (i) pomegranate juice (which has some antioxidant properties) administered to Tg2576 mice for 6 mo had no effect on CAA formation (63); (ii) curcumin (which has some antioxidant properties) administered to APP/PS1 dE9 mice for 7 d had a nonsignificant trend toward reducing CAA formation (62); and (iii) phenyl-N-tert-butyl nitrone (a nonspecific ROS scavenger) given to APP/PS1 dE9 and Tg2576 mice for 1 mo had no effect on CAA formation (36). Again, issues of potency, specificity, and duration of therapy could have affected these results.…”

Section: Discussionmentioning

confidence: 99%

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Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Han

Zhou

Johnson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

112

103

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Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid β peptide (Aβ) within walls of cerebral arteries and is an important cause of intracerebral hemorrhage, ischemic stroke, and cognitive dysfunction in elderly patients with and without Alzheimer's Disease (AD). NADPH oxidase-derived oxidative stress plays a key role in soluble Aβ-induced vessel dysfunction, but the mechanisms by which insoluble Aβ in the form of CAA causes cerebrovascular (CV) dysfunction are not clear. Here, we demonstrate evidence that reactive oxygen species (ROS) and, in particular, NADPH oxidase-derived ROS are a key mediator of CAA-induced CV deficits. First, the NADPH oxidase inhibitor, apocynin, and the nonspecific ROS scavenger, tempol, are shown to reduce oxidative stress and improve CV reactivity in aged Tg2576 mice. Second, the observed improvement in CV function is attributed both to a reduction in CAA formation and a decrease in CAA-induced vasomotor impairment. Third, anti-ROS therapy attenuates CAA-related microhemorrhage. A potential mechanism by which ROS contribute to CAA pathogenesis is also identified because apocynin substantially reduces expression levels of ApoE-a factor known to promote CAA formation. In total, these data indicate that ROS are a key contributor to CAA formation, CAA-induced vessel dysfunction, and CAA-related microhemorrhage. Thus, ROS and, in particular, NADPH oxidase-derived ROS are a promising therapeutic target for patients with CAA and AD.Alzheimer's disease | cerebral amyloid angiopathy | reactive oxygen species | NADPH oxidase | vasomotor dysfunction

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Han

Zhou

Johnson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

112

103

View full text Add to dashboard Cite

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“…In addition to its strong antioxidant ability, it has anti-inflammatory activity, reduces amyloid plaque burden, and partially restored distorted neuritis [125][126][127][128]. A current Phase II clinical trial that combines curcumin and yoga therapy aims to treat MCI (ClinicalTrials.gov identifier: NCT01811381).…”

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

2015

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Alzheimer's disease (AD) has a complex and progressive neurodegenerative phenotype, with hypometabolism and impaired mitochondrial bioenergetics among the earliest pathogenic events. Bioenergetic deficits are well documented in preclinical models of mammalian aging and AD, emerge early in the prodromal phase of AD, and in those at risk for AD. This review discusses the importance of early therapeutic intervention during the prodromal stage that precedes irreversible degeneration in AD. Mechanisms of action for current mitochondrial and bioenergetic therapeutics for AD broadly fall into the following categories: 1) glucose metabolism and substrate supply; 2) mitochondrial enhancers to potentiate energy production; 3) antioxidants to scavenge reactive oxygen species and reduce oxidative damage; 4) candidates that target apoptotic and mitophagy pathways to either remove damaged mitochondria or prevent neuronal death. Thus far, mitochondrial therapeutic strategies have shown promise at the preclinical stage but have had little-to-no success in clinical trials. Lessons learned from preclinical and clinical therapeutic studies are discussed. Understanding the bioenergetic adaptations that occur during aging and AD led us to focus on a systems biology approach that targets the bioenergetic system rather than a single component of this system. Bioenergetic system-level therapeutics personalized to bioenergetic phenotype would target bioenergetic deficits across the prodromal and clinical stages to prevent and delay progression of AD.

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“…Curcumin has also been found to lower amyloid-β protein levels by attenuating the maturation of APP in the secretory pathway. Curcumin was demonstrated to promote a significant reversal of structural changes in dystrophic dendrites, including abnormal curvature and dystrophy size (13). The computed ionization potential and electron affinity show that curcumin has a low-molecular hardness, and the resulting charge undergoes delocalization throughout the structure, resulting in excitonic features.…”

Section: Resultsmentioning

confidence: 99%

Turmeric and curcumin suppress presenilin 1 protein expression in Jurkat cells

Yoshida¹,

Okumura²,

Nishimura³

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. In the present study, we aimed to determine the effects of herbs or spices on the expression of presenilin 1, a molecule involved in γ-secretase activity and the generation of amyloid-β peptide in Alzheimer's disease. Western blot analysis revealed that presenilin 1 protein expression was down-regulated by stimulation with turmeric or cinnamon extracts in vitro, while the effects on presenilin 1 gene expression examined by reverse transcriptase-polymerase chain reaction were unaltered. Our results showed that curcumin, a component of turmeric, induced the down-regulation of presenilin 1 protein in Jurkat and K562 cell lines. IntroductionAlzheimer's disease is a neurodegenerative disease caused by amyloid-β accumulation in brain cells combined with oxidative stress and inflammation (1,2). Neurotoxic amyloid-β is an approximately 4-kDa peptide generated via cleavage of the amyloid-β precursor protein (APP) by the γ-secretase proteolytic complex (3). Presenilin is the catalytic member of the γ-secretase complex, and mutations in presenilin are the major cause of early-onset familial Alzheimer's disease. Presenilin is involved in several biological functions, but is well known for its role in the generation of the amyloid-β peptide in Alzheimer's disease and is therefore thought to be an important drug target for this disorder. Thus, an increased understanding of Presenilin may help to improve the development of drugs for Alzheimer's disease and for other neurological diseases (4).Certain herbs have been demonstrated to possess a multitude of beneficial activities, and herbal medications are currently being used for widespread clinical use in disease therapy, as herbs exhibit relatively mild bioavailability and low toxicity (5). As for Alzheimer's disease, polyphenols extracted from grape seeds have been found to inhibit amyloid-β aggregation, reduce amyloid-β production and protect against amyloid-β neurotoxicity in vitro (6,7). In addition, cryptotanshinone (CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several pharmacological models of Alzheimer's disease (8). Further research demonstrated that CTS improved the cognitive ability and promoted APP metabolism involving the non-amyloidogenic product pathway in rat cortical neuronal cells. Moreover, as the Indian diet is rich in herbs and spices, the incidence of Alzheimer's disease in India is considerably low (9,10). However, the precise molecular mechanisms of the therapeutic effects of medicinal herbs and spices are largely undefined, and limited data and a small body of convincing evidence exist at the molecular level (11). Therefore, basic research and development aimed at elucidating the mechanism of action underlying herbal effects should have high priority. We hypothesized that various herbs or spices may affect the γ-secretase proteolytic function. Therefore, we investigated the in vitro effect of several herbs on the expression of presenilin 1 in cultured human cells. Material...

show abstract

Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model

Cited by 614 publications

References 45 publications

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

Turmeric and curcumin suppress presenilin 1 protein expression in Jurkat cells

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