Binding of Curcumin to Senile Plaques and Cerebral Amyloid Angiopathy in the Aged Brain of Various Animals and to Neurofibrillary Tangles in Alzheimer's Brain

ArticleinJournal of Veterinary Medical Science 74(1):51-7 · September 2011with26 Reads
DOI: 10.1292/jvms.11-0307 · Source: PubMed
The binding of curcumin to senile plaques (SPs) and cerebral amyloid angiopathy (CAA) was examined in the aged brain of various animal species and a human patient with Alzheimer's disease (AD), together with its binding to neurofibrillary tangles (NFTs). Brain sections were immunostained with anti-amyloid β protein 1-42 (Aβ42) and anti-amyloid β protein 1-40 (Aβ40) antibodies. These sections were also stained with alkaline Congo red, periodic acid-methenamine silver (PAM), and curcumin (0.009% curcumin solution) with or without formic acid pretreatment. The sections from the AD brain were also immunostained for anti-paired helical filament-tau (PHF-tau), and were stained with Gallyas silver for NFTs. Some SPs in the AD, monkey, dog, bear, and amyloid precursor protein transgenic mouse (APP Tg-mouse) brains contained congophilic materials, and were intensely positive for curcumin. In addition, curcumin labeled some diffuse SPs negative for Congo red in the AD, monkey, bear, and APP Tg-mouse brains. In all animals, CAA was intensely positive for both Congo red and curcumin. The specific curcumin staining activity was lost by formic acid pretreatment. In the AD brain, NFTs positive for PHF-tau and Gallyas silver were moderately stained with curcumin. These findings indicate that curcumin specifically binds to the aggregated Aβ molecules in various animals, and further to phosphorylated tau protein, probably according to its conformational nature.
    • "Whereas, we found " curcumin " as a natural anti-amyloid polyphenol, which have potential role to inhibit misfolded protein aggregation, and also restore protein clearance pathways [8,24], which are discuss further below. Inhibition of Aβ production Inhibit activation of β-secretase (BACE), inhibiting amyloid precursor protein (APP) processing pathway [13,24] Aβ clearance Stimulate phagocytosis, thus decrease Aβ-plaques [11,26,27] Inhibition of NFTs Bind with NFTs and inhibits tau phosphorylation (pTau) [28] Inhibition of other amyloid Bind with α-synuclein in PD, huntingtin in HD and prion aggregates in prion disease [14,29] Potent Antioxidant: Scavenges ROS/RONS, increase antioxidant levels, decrease lipid peroxidation, chelate toxic metals. [26,27,30] Anti-inflammatory activity: Down regulate NF-κB, COX-2, 5-LOX, TNF, IL-1, IL-6. "
    Article · Dec 2015 · PLoS ONE
    • "We next characterized the ability of curcumin to bind to LBs in diseased human brain tissue. Previous data has shown that curcumin labels human A-beta plaques and neurofibrillary tangles , suggesting a specific preference for proteins in a beta-sheet rich amyloid confirmation, similar to dyes such as Thioflavin-S/T and Congo Red [5,17,18]. Because human brain tissue contains significant amounts of lipofuscin autofluorescence, which overlaps with the broad curcumin emission spectrum, we found that spectral imaging combined with linear unmixing was useful to accurately detect curcumin staining above the autofluorescent background in the tissue. "
    [Show abstract] [Hide abstract] ABSTRACT: The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ∼5 ng/mL and ∼12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease.
    Full-text · Article · Jun 2015
    • "Curcumin can also reduce Aβ production by inhibiting beta secretase (BACE), the enzyme responsible for synthesis of Aβ from amyloid precursor protein79808182. It also decreases Aβ production by inhibiting GSK-3β (the enzyme responsible for phosphorylation of tau) mediated presinilin-1 activation [83]. It can also stimulate phagocytosis of Aβ in a rat AD model [33]. "
    Article · Jan 2014 · PLoS ONE
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