scholarly journals Computer-assisted evaluation of plant-derived β-secretase inhibitors in Alzheimer’s disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Md. Asad Ullah ◽  
Fatema Tuz Johora ◽  
Bishajit Sarkar ◽  
Yusha Araf ◽  
Nafisa Ahmed ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ellagic Acid ◽  
Biological Activities ◽  
Memory Loss ◽  
Computer Assisted ◽  
Age Related ◽  
Secretase Inhibitor

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative age-related dementia that results in memory loss of elderly people. Many hypotheses have been formally articulated till now to decipher the pathogenesis of this disease. According to the compelling amyloidogenic hypothesis, β-secretase is a key regulatory enzyme in AD development and is therefore considered as one of the major targets for the development of drugs to treat AD. In this study, 40 plant-derived phytocompounds, proven to have β-secretase inhibitory activity in different laboratory experiments, were evaluated using computational approaches in order to identify the best possible β-secretase inhibitor(s). Results Amentoflavone (IFD score: − 7.842 Kcal/mol), Bilobetin (IFD score: − 7.417 Kcal/mol), and Ellagic acid (IFD score: − 6.923 Kcal/mol) showed highest β-secretase inhibitory activities with high binding affinity among all the selected phytocompounds and interacted with key amino acids, i.e., Asp32, Tyr71, and Asp228 in the catalytic site of β-secretase. Moreover, these three molecules exhibited promising results in different drug potential assessment experiments and displayed signs of correlation with significant pharmacological and biological activities. Conclusion Amentoflavone, Biolbetin, and Ellagic acid could be investigated further in developing β-secretase-dependent drug for the effective treatment of AD. However, additional in vivo and in vitro experiments might be required to strengthen the findings of this experiment.

scholarly journals SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer’s Disease Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1275
Author(s):  
Soo Yong Park ◽  
Joo Yeong Kang ◽  
Taehee Lee ◽  
Donggyu Nam ◽  
Chang-Jin Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Physiological Activity ◽  
Precursor Protein ◽  
Age Related

Alzheimer’s disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (Aβ) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of Aβ, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in Aβ reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of Aβ when co-cultured with Aβ-secreting Neuro 2a cells. The human SPON1 gene itself also reduced Aβ in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of Aβ and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.

Extraction of Polysaccharides From Bletilla Striata Using a Modified Low-temperature Method and Evaluation of Their Efficacy Against Alzheimer’s Disease

2021 ◽  
Author(s):  
Yi-Wen Lin ◽  
Chih-Hsiang Fang ◽  
Hung-Hsiang Liao ◽  
Feng Huei Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Low Temperature ◽  
Memory Loss ◽  
Amyloid Β ◽  
Ulcer Bleeding ◽  
Bletilla Striata ◽  
Temperature Method

Abstract Background: Amyloid-β (Aβ) peptides play a key role in Alzheimer’s disease (AD), the most common type of dementia. AD is characterized by progressive cognitive and memory loss accompanied by personality changes. Bletilla striata, a traditional Chinese medicine, has been widely used in Eastern Asian countries for alimentary canal damage, ulcer, bleeding, bruises, and burns. in this study, we investigated whether BSP could prevent the ROS from Aβ and the possibility to recover from the disease by memory improvement.Methods: In this study, a polysaccharide from Bletilla striata (BSP) with strong antioxidant and anti-inflammatory properties was extracted following a low-temperature method and tested for its efficacy against AD in vitro using N2a and BV-2 cells and in vivo using AD rats.Results: The characterization of the extracted BSP for its molecular structure and the functional group demonstrated the efficiency of the modified method to retain its bioactivity. In vitro, BSP reduced ROS levels in N2a cells and the expression levels of inflammatory-related genes in BV-2 cells treated with Aβ fibrils. In vivo, BSP recovered the learning memory, ameliorated the morphological damages in the hippocampus and cortex, and reduced the expression of the β-secretase protein in AlCl3-induced AD rats.Conclusions: To the best of our knowledge, this is the first study of BSP applicating in AD. Collectively, these findings demonstrated the efficacy of BSP to prevent and alleviate the effects of AD.

scholarly journals Optimized-SopungSunkiwon, a Herbal Formula, Attenuates AβOligomer-Induced Neurotoxicity in Alzheimer’s Disease Models

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jin Gyu Choi ◽  
Sun Yeou Kim ◽  
Jong Woo Kim ◽  
Myung Sook Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Medicinal Herbs ◽  
Glutathione Depletion ◽  
Age Related

Alzheimer’s disease (AD), the most common form of dementia, is an age-related neurodegenerative disease that is characterized by memory dysfunction, neuronal cell damage, and neuroinflammation. It is believed that AD-related pathology is mostly due to the overproduction of Aβ, especially the oligomeric form (AβO), in the brain. Evidence of the effects of multifunctional medicinal herbs in the treatment of AD has been steadily increasing. Optimized-SopungSunkiwon (OSS), a multiherbal formulation that is composed of six medicinal herbs derived from SopungSunkiwon, is a traditional medicine that is prescribed for neurodegenerative disorders in elderly patients. We previously reported that OSS showed an antiamnesic and memory enhancing effect in mice, but it is unknown whether OSS has a protective effect against AβO neurotoxicity. In this study, we investigated the effects of OSS in AD models induced by AβOin vitroandin vivo. We found that OSS protected neuronal cells and inhibited the generation of nitric oxide and reactive oxygen species against AβO toxicityin vitro. These results were confirmed byin vivodata that oral administration of OSS for 14 days attenuated memory impairments and neuronal cell death by modulating gliosis, glutathione depletion, and synaptic damage in the mouse hippocampus induced by AβO.

scholarly journals The Combination of β-Asarone and Icariin Inhibits Amyloid-β and Reverses Cognitive Deficits by Promoting Mitophagy in Models of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Nanbu Wang ◽  
Haoyu Wang ◽  
Qi Pan ◽  
Jian Kang ◽  
Ziwen Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Combination Therapy ◽  
Cognitive Deficits ◽  
Amyloid Β ◽  
In Vivo Models ◽  
Age Related ◽  
The Individual

β-Asarone is the main constituent of Acorus tatarinowii Schott and exhibits important effects in diseases such as neurodegenerative and neurovascular diseases. Icariin (ICA) is a major active ingredient of Epimedium that has attracted increasing attention because of its unique pharmacological effects in degenerative disease. In this paper, we primarily explored the effects of the combination of β-asarone and ICA in clearing noxious proteins and reversing cognitive deficits. The accumulation of damaged mitochondria and mitophagy are hallmarks of aging and age-related neurodegeneration, including Alzheimer’s disease (AD). Here, we provide evidence that autophagy/mitophagy is impaired in the hippocampus of APP/PS1 mice and in Aβ1-42-induced PC12 cell models. Enhanced mitophagic activity has been reported to promote Aβ and tau clearance in in vitro and in vivo models. Meanwhile, there is growing evidence that treatment of AD should be preceded by intervention before the formation of pathological products. The efficacy of the combination therapy was better than that of the individual therapies applied separately. Then, we found that the combination therapy also inhibited cell and mitochondrial damage by inducing autophagy/mitophagy. These findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis, and that combination treatment with mitophagy inducers represents a potential strategy for therapeutic intervention.

Survival signalling in Alzheimer's disease

2006 ◽  
Vol 34 (6) ◽  
pp. 1277-1282 ◽  
Author(s):  
W.J. Lukiw ◽  
N.G. Bazan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acid ◽  
Cell Survival ◽  
Plasma Membranes ◽  
Enzymatic System ◽  
Neuroprotectin D1 ◽  
Age Related

Significant advancements in our understanding of cell-survival signalling in AD (Alzheimer's disease) stem from recent investigations into the metabolism, trafficking and fate of the essential ω-3 fatty acid DHA (docosahexaenoic acid) (C22:6, n=3). Brain synaptic terminals and neuronal plasma membranes are highly enriched in DHA, and deficiencies in this polyunsaturated fatty acid are characteristic of AD-affected brain. Oxidative stress, targeting phospholipids containing DHA, and age-related DHA depletion are associated with the progressive erosion of normal cognitive function in AD. Current studies support the idea that DHA itself and novel DHA-derived neural synapse- and membrane-derived lipid messengers have considerable potential to modulate cell survival signalling in stressed cultured neural cell models in vitro and in mammalian models of learning, memory and AD in vivo. Key players in this intrinsic rescue system include the α-secretase-processed neurotrophin sAPPα [soluble APPα (amyloid precursor protein α)] peptide, the DHA-derived 10,17S-docosatriene NPD1 (neuroprotectin D1), a tandem brain cytosolic phospholipase A2 and 15-lipoxygenase enzymatic system that biosynthesizes NPD1, and a small family of anti-apoptotic neuroprotective genes that encode Bcl-2, Bcl-XL and Bfl-1 (A1). This paper reviews current ideas regarding DHA and the oxygenated DHA derivative NPD1, intrinsically triggered biolipid neuroprotectants that along with their associated rescue pathways, contribute to life-or-death decisions of brain cells during homoeostasis, aging and neurodegenerative disease.

scholarly journals Jowiseungchungtang Inhibits Amyloid-β Aggregation and Amyloid-β-Mediated Pathology in 5XFAD Mice

2018 ◽  
Vol 19 (12) ◽  
pp. 4026 ◽  
Author(s):  
Soo Shin ◽  
Yu-on Jeong ◽  
Seong Jeon ◽  
Sujin Kim ◽  
Seong-kyung Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Amyloid Β ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Aβ Aggregation ◽  
5Xfad Mice

Alzheimer’s disease (AD) is a neurodegenerative disease, which is accompanied by memory loss and cognitive dysfunction. Although a number of trials to treat AD are in progress, there are no drugs available that inhibit the progression of AD. As the aggregation of amyloid-β (Aβ) peptides in the brain is considered to be the major pathology of AD, inhibition of Aβ aggregation could be an effective strategy for AD treatment. Jowiseungchungtang (JWS) is a traditional oriental herbal formulation that has been shown to improve cognitive function in patients or animal models with dementia. However, there are no reports examining the effects of JWS on Aβ aggregation. Thus, we investigated whether JWS could protect against both Aβ aggregates and Aβ-mediated pathology such as neuroinflammation, neurodegeneration, and impaired adult neurogenesis in 5 five familial Alzheimer’s disease mutations (5XFAD) mice, an animal model for AD. In an in vitro thioflavin T assay, JWS showed a remarkable anti-Aβ aggregation effect. Histochemical analysis indicated that JWS had inhibitory effects on Aβ aggregation, Aβ-induced pathologies, and improved adult hippocampal neurogenesis in vivo. Taken together, these results suggest the therapeutic possibility of JWS for AD targeting Aβ aggregation, Aβ-mediated neurodegeneration, and impaired adult hippocampal neurogenesis.

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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