Amelioration effects of Cirsium japonicum var. maackii extract/fractions on amyloid beta25–35-induced neurotoxicity in SH-SY5Y cells and identification of the main bioactive compound

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.

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The Challenges of Diagnosis in Alzheimer’s Disease

US Neurology ◽

10.17925/usn.2018.14.1.15 ◽

2018 ◽

Vol 14 (1) ◽

pp. 15 ◽

Cited By ~ 1

Author(s):

Nenad Bogdanovic

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Amyloid Pet ◽

Positive Finding ◽

Positron Emission ◽

University Of Oslo ◽

The University ◽

Study Participants ◽

The Brain

Current neuropathologic examination of the brain is still the gold standard for diagnosis of Alzheimer’s disease (AD). Postmortem studies, however, have indicated that current methods for the clinical diagnosis of AD are suboptimal.1Recent research has demonstrated the clinical utility of amyloid-beta positron emission tomography (PET) scans, which detect the presence of amyloid-beta plaques in the brain. In a study presented at the Alzheimer’s Association International Conference (AAIC) in London, UK, July 2017, by Nenad Bogdanovic, MD, PhD, of the University of Oslo in Norway, amyloid PET imaging was found to be a fundamental diagnostic tool for AD, establishing a definite diagnosis or excluding AD in all 50 study participants.2 The use of cerebrospinal fluid (CSF) amyloid testing with a higher amyloid-beta plaque threshold than that traditionally used to establish a positive finding also resulted in high diagnostic accuracy, resulting in diagnosis or exclusion in 44 of 50 participants (88%) compared with only 21 individuals (42%) using traditional cutoffs.2

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Melanoma-secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis

10.1101/854885 ◽

2019 ◽

Author(s):

Kevin Kleffman ◽

Grace Levinson ◽

Eitan Wong ◽

Francisco Galán-Echevarría ◽

Richard Von-Itter ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Metastasis ◽

Amyloid Beta ◽

Metastatic Cancer ◽

Melanoma Cells ◽

Brain Parenchyma ◽

Multiple Cancer ◽

Cancer Types ◽

The Brain

SummaryBrain metastasis is a significant cause of morbidity and mortality in multiple cancer types and represents an unmet clinical need. The mechanisms that mediate metastatic cancer growth in the brain parenchyma are largely unknown. Melanoma, which has the highest rate of brain metastasis among common cancer types, is an ideal model to study how cancer cells adapt to the brain parenchyma. We performed unbiased proteomics analysis of melanoma short-term cultures, a novel model for the study of brain metastasis. Intriguingly, we found that proteins implicated in neurodegenerative pathologies are differentially expressed in melanoma cells explanted from brain metastases compared to those derived from extracranial metastases. This raised the exciting hypothesis that molecular pathways implicated in neurodegenerative disorders are critical for metastatic adaptation to the brain.Here, we show that melanoma cells require amyloid beta (Aβ), a polypeptide heavily implicated in Alzheimer’s disease, for growth and survival in the brain parenchyma. Melanoma cells produce and secrete Aβ, which activates surrounding astrocytes to a pro-metastatic, anti-inflammatory phenotype. Furthermore, we show that pharmacological inhibition of Aβ decreases brain metastatic burden.Our results reveal a mechanistic connection between brain metastasis and Alzheimer’s disease – two previously unrelated pathologies, establish Aβ as a promising therapeutic target for brain metastasis, and demonstrate suppression of neuroinflammation as a critical feature of metastatic adaptation to the brain parenchyma.

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The Importance of Understanding Amylin Signaling Mechanisms for Therapeutic Development in the Treatment of Alzheimer’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612826666200318151146 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1345-1355 ◽

Cited By ~ 2

Author(s):

Spencer Servizi ◽

Rachel R. Corrigan ◽

Gemma Casadesus

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Signaling Cascades ◽

Complex Nature ◽

Amyloid Accumulation ◽

Therapeutic Development ◽

Critical Insight ◽

The Brain

Type II Diabetes (T2D) is a major risk factor for Alzheimer’s Disease (AD). These two diseases share several pathological features, including amyloid accumulation, inflammation, oxidative stress, cell death and cognitive decline. The metabolic hormone amylin and amyloid-beta are both amyloids known to self-aggregate in T2D and AD, respectively, and are thought to be the main pathogenic entities in their respective diseases. Furthermore, studies suggest amylin’s ability to seed amyloid-beta aggregation, the activation of common signaling cascades in the pancreas and the brain, and the ability of amyloid beta to signal through amylin receptors (AMYR), at least in vitro. However, paradoxically, non-aggregating forms of amylin such as pramlintide are given to treat T2D and functional and neuroprotective benefits of amylin and pramlintide administration have been reported in AD transgenic mice. These paradoxical results beget a deeper study of the complex nature of amylin’s signaling through the several AMYR subtypes and other receptors associated with amylin effects to be able to fully understand its potential role in mediating AD development and/or prevention. The goal of this review is to provide such critical insight to begin to elucidate how the complex nature of this hormone’s signaling may explain its equally complex relationship with T2D and mechanisms of AD pathogenesis.

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GINKGETIN AMELIORATES NEUROPATHOLOGICAL CHANGES IN APP/PS1 TRANSGENICAL MICE MODEL

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2015.84 ◽

2015 ◽

pp. 1-6

Author(s):

Y.-Q. Zeng ◽

Y.-J. Wang ◽

X.-F. Zhou

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Biological Properties ◽

Amyloid Angiopathy ◽

Amyloid Beta Protein ◽

Mice Model ◽

Cerebral Microhemorrhage ◽

The Brain

The extracellular accumulation of amyloid beta protein (Aβ), reactive gliosis and cerebral amyloid angiopathy (CAA) play critical roles in the pathogenesis of Alzheimer’s disease (AD). Ginkgetin, a biflavone isolated from Ginkgo biloba leaves, was previously reported to exhibit strong neuroprotection against cytotoxic insults induced by oxidative stress and amyloid beta, but it remains unclear whether ginkgetin has therapeutic effect on Alzheimer’s disease (AD) in vivo. In the present study, we investigated 9 months treatment effects of ginkgetin diet in APP/PS1 mice. Our results show that ginkgetin can significantly reduce plasma Aβ levels 59% and Aβ plaque 51% in the brain of APP/PS1 transgenic mice (P<0.05), effectively inhibits cerebral microhemorrhage 69% (P<0.05), significantly decreases astrogliosis 50% and ameliorate inflammation (P<0.05), exhibits several biological properties for AD.

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