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.
ABSTRACT 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.
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ABSTRACT: The lack of an adequate therapy for Alzheimer's Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm "Multi-Target-Directed Ligands" (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.Current Neuropharmacology 01/2014; 12(1):2-36. · 2.03 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.Current Neuropharmacology 07/2013; 11(4):414-29. · 2.03 Impact Factor
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ABSTRACT: Abstract Senile plaques (SPs) and cerebral amyloid angiopathy (CAA) consisting of β-amyloid (Aβ) are major features in the brain of Alzheimer's disease (AD) patients and elderly humans and animals. In this study, we report the finding of SPs and CAA in an aged sea lion (30 years), which is the first demonstration of AD-related pathological changes in a marine animal. Histologically, SPs were observed at the cerebral cortex, most frequently at the frontal lobe, with two morphologically different types: the small round type and the large granular type. Only the small round SPs were positive for Congo red staining. The SPs were equally immunoreactive to Aβ40 and Aβ42 and were mainly composed of Aβ with an N-terminal pyroglutamate residue at position 3. Amyloid depositions at vessel walls were noted at the meninges and within the parenchyma. Interestingly, double immunofluorescence staining for Aβ40 and Aβ42 showed that the two subtypes were deposited segmentally in different parts of the vessel walls. The lesions observed in the sea lion suggest that Aβ deposition is widely present in various animal species, including marine mammals; however, the peculiar deposits similar to cotton wool plaques and the specific pattern of CAA are characteristic features of this animal.Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 04/2014; · 2.51 Impact Factor