scholarly journals Annona atemoya leaf extract ameliorates cognitive impairment in amyloid-β injected Alzheimer’s disease-like mouse model

2019 ◽  
Vol 244 (18) ◽  
pp. 1665-1679 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Eunjin Sohn ◽  
Jiyeon Yoon ◽  
Bu-Yeo Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Cell Death ◽  
Growth Factor Receptor ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Bioactive Compound ◽  
Aβ Aggregation ◽  
Epidermal Growth ◽  
G Protein Coupled

Annona atemoya is a hybrid of Annona squamosa and Annona cherimola that grow in several subtropical or tropical areas such as Florida in the US, Philippines, Cuba, Jamaica, Taiwan, and Jeju in South Korea. We report that the A. atemoya leaves (AAL) have inhibitory effects on the pathogenesis and regulatory mechanisms of Alzheimer’s disease (AD). Ethanol extract of AAL prevented amyloid-β (Aβ) aggregation and increased free radical scavenging activity. In addition, AAL extract exerted protective effects against neuronal cell death in HT22 hippocampal cells. Moreover, oral administration of AAL extract significantly improved memory loss in the passive avoidance task and Y-maze test, as well as downregulated the expression of neuronal markers neuronal nuclei and brain-derived neurotrophic factor in Aβ-injected AD mice. To verify the molecular mechanisms responsible for anti-AD actions of AAL, we conducted the antibody microarray analysis and found that epidermal growth factor receptor/G protein-coupled receptor kinase 2 signaling was activated in neuronal cells and AD-like mouse models. Additionally, quantitative analyses of the six standard compounds using high-performance liquid chromatography revealed that rutin is the most abundant compound of AAL. Furthermore, efficacy analyses of six standard compounds showed that rutin and isoquercitrin had significant inhibitory activity on Aβ aggregation. Taken together with biological activity and the content of compounds, rutin maybe a bioactive compound of AAL in the AD pathogenesis. Overall, our findings provide the first scientific support for the therapeutic effects of AAL in AD and AD-related disorders. Impact statement Our study was aimed to find a novel candidate drug for Alzheimer’s disease (AD) using natural products. We assessed the effects of Annona atemoya extracts on crucial events in the pathogenesis of AD. A. atemoya leaf (AAL) extract significantly inhibited amyloid-β aggregation, oxidative stress, neuronal cell death, and memory impairment through the epidermal growth factor receptor/G protein-coupled receptor kinase 2 pathway. Simultaneous analysis using HPLC determined six standard compounds of AAL extract, and rutin was identified as a bioactive compound. Of note, the anti-AD activity of AAL extract was more significant compared to other extracts from medicinal plants of which efficacy was previously reported. The potential of AAL extract as an anti-AD agent may provide insight into the new drug development for AD treatment.

Disease modifying strategies for the treatment of Alzheimer's disease targeted at modulating levels of the β-amyloid peptide

2005 ◽  
Vol 33 (4) ◽  
pp. 553-558 ◽  
Author(s):  
M.N. Pangalos ◽  
S.J. Jacobsen ◽  
P.H. Reinhart
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Proteolytic Processing ◽  
Amyloid Peptide ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid ◽  
Disease Modifying

AD (Alzheimer's disease) is characterized neuropathologically by the presence of amyloid plaques, neurofibrillary tangles and profound grey matter loss. The ‘amyloid’ hypothesis postulates that the toxic Aβ (amyloid β) peptide, enzymatically derived from the proteolytic processing of a larger protein called APP (amyloid precursor protein), is one of the principal causative factors of neuronal cell death in the brains of AD patients. As such, methods for lowering Aβ levels in the brain are of significant interest with regard to identifying novel disease modifying therapies for the treatment of AD. In this review, we will review a variety of approaches and mechanisms capable of modulating levels of Aβ.

scholarly journals Simultaneous Quantification of Four Marker Compounds in Bauhinia coccinea Extract and Their Potential Inhibitory Effects on Alzheimer’s Disease Biomarkers

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 702
Author(s):  
Yu Jin Kim ◽  
Eunjin Sohn ◽  
Hye-Sun Lim ◽  
Yoonju Kim ◽  
Joo-Hwan Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gallic Acid ◽  
Biological Activities ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Interactive Effects ◽  
Inhibitory Effects ◽  
Aβ Aggregation ◽  
Marker Compounds

Bauhinia coccinea is a tropical woody plant widely distributed in Vietnam and Unnan in southern China. Although many studies have shown the biological activities of extracts from various other species in the genus, no studies have investigated the effects of B. coccinea extracts on biological systems. In the present study, a quantitative analysis of four marker compounds of ethanol extracts of B. coccinea branches (EEBC) was performed using the high performance liquid chromatography (HPLC)-photodiode array (PDA) method. Among gallic acid, (+)-catechin, ellagic acid, and quercitrin contained in EEBC, the most abundant compound was (+)-catechin (18.736 mg/g). In addition, we investigated the EEBC on neuroprotection, antioxidation, and Alzheimer’s disease (AD) marker molecules, acetylcholinesterase (AChE), and amyloid-β (Aβ). EEBC significantly inhibited hydrogen peroxide (H2O2)-induced cell death in a HT22 neuronal cell line and increased 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl scavenging activity markedly. EEBC also inhibited AChE and Aβ aggregation. Among the four compounds, gallic acid exhibited strong inhibitory effects against AChE activation. In the Aβ aggregation assay, the four marker compounds exhibited inhibitory effects lower than 30%. According to the results, EEBC could exert anti-AChE activation and Aβ aggregation activities based on the interactive effects of the marker compounds. Our findings suggest that EEBC are sources of therapeutic candidates for application in the development of AD medication based on AChE and Aβ dual targeting.

scholarly journals Alzheimer’s disease as an inflammatory disease

2017 ◽  
Vol 8 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Marta Bolós ◽  
Juan Ramón Perea ◽  
Jesús Avila
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Short Review ◽  
Hyperphosphorylated Tau ◽  
Progressive Dementia ◽  
Hyperphosphorylated Tau Protein

AbstractAlzheimer’s disease (AD) is a neurodegenerative condition characterized by the formation of amyloid-β plaques, aggregated and hyperphosphorylated tau protein, activated microglia and neuronal cell death, ultimately leading to progressive dementia. In this short review, we focus on neuroinflammation in AD. Specifically, we describe the participation of microglia, as well as other factors that may contribute to inflammation, in neurodegeneration.

scholarly journals Microglia-Derived Interleukin 23: A Crucial Cytokine in Alzheimer's Disease?

2021 ◽  
Vol 12 ◽  
Author(s):  
Louisa Nitsch ◽  
Linda Schneider ◽  
Julian Zimmermann ◽  
Marcus Müller
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Plaque Formation ◽  
Immune Mediators ◽  
Inflammatory Processes ◽  
Interleukin 23

Neuronal cell death, amyloid β plaque formation and development of neurofibrillary tangles are among the characteristics of Alzheimer's disease (AD). In addition to neurodegeneration, inflammatory processes such as activation of microglia and astrocytes are crucial in the pathogenesis and progression of AD. Cytokines are essential immune mediators of the immune response in AD. Recent data suggest a role of interleukin 23 (IL-23) and its p40 subunit in the pathogenesis of AD and corresponding animal models, in particular concerning microglia activation and amyloid β plaque formation. Moreover, in animal models, the injection of anti-p40 antibodies resulted in reduced amyloid β plaque formation and improved cognitive performance. Here, we discuss the pathomechanism of IL-23 mediated inflammation and its role in AD.

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

2020 ◽  
Vol 26 ◽  
Author(s):  
Nimra Javaid ◽  
Muhammad Ajmal Shah ◽  
Azhar Rasul ◽  
Zunera Chauhdary ◽  
Uzma Saleem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ellagic Acid ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acetylcholinesterase Activity ◽  
Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease

2020 ◽  
Vol 20 (26) ◽  
pp. 2380-2390 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Abdullah Al Mamun ◽  
Md. Ataur Rahman ◽  
Tapan Behl ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Misfolding ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Misfolded Proteins ◽  
Cell Organelles ◽  
The Impact

Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD. Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now. Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.

scholarly journals Heparan sulphate compounds regulate cholesterol metabolism in neurodegenerative disease models

2021 ◽  
Author(s):  
◽  
Rosemary Heathcott
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Cell Line ◽  
Cholesterol Metabolism ◽  
Neurodegenerative Disorder ◽  
Heparan Sulphate ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Lysosomal Storage

<p>Heparan sulphate proteoglycans (HSPG) are central to numerous processes of the mammalian cell. The highly charged negative side chains of the heparan sulphate (HS) oligosaccharides are essential for the regulatory and structural functions of the proteoglycan. Synthetic HS compounds have potential therapeutic value due to their ability to mimic naturally occurring HS. Niemann-Pick disease type C (NPC) is a fatal childhood neurodegenerative disease with characteristic cholesterol and sphingolipid accumulation in the late endosome or lysosome. Alzheimer’s disease, another neurodegenerative disorder, shares alterations of cholesterol and amyloid β metabolism with NPC. In this study,a set of novel heparan sulphate compounds with a range of structures and oligosaccharide side groups with a variety of degrees of sulphation was investigated with regards to their effects on cholesterol and amyloid β metabolism in cell line models of these two diseases. Fluorescent staining of cholesterol and confocal microscopy showed highly sulphated compounds reduce the accumulation of cholesterol in the perinuclear lysosomal storage organelles in patient fibroblast cell lines. The compounds had no effect on secreted amyloid β levels or amyloid precursor protein levels in a neuronal cell line model of early onset Alzheimer’s disease. The mechanism of cholesterol reduction is unclear but may be related to a reduction in HSPG-associated endocytosis of LDL/cholesterol.</p>

scholarly journals Cu-Based Turn-on Fluorescent Sensors for Cu-rich Amyloid β Aggregates

2021 ◽  
Author(s):  
Yiran Huang ◽  
Liang Sun ◽  
Liviu M. Mirica
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fluorescence Imaging ◽  
Protein Misfolding ◽  
Picolinic Acid ◽  
Amyloid Β ◽  
Fluorescent Sensors ◽  
Aβ Oligomers ◽  
Turn On ◽  
Aβ Aggregation

<div>Protein misfolding and metal dishomeostasis are two key</div><div>pathological factors of Alzheimer’s disease. Previous studies have showed that Cu‐mediated Aβ aggregation pathways lead to formation of neurotoxic Aβ oligomers. Herein, we reported a series of picolinic acid‐based Cu‐activatable sensors, which can be used for the fluorescence imaging of Cu‐rich Aβ aggregates.</div>

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