Small Molecule Natural Products and Alzheimer’s Disease

2019 ◽  
Vol 19 (3) ◽  
pp. 187-204 ◽  
Author(s):  
Xiaoai Wu ◽  
Huawei Cai ◽  
Lili Pan ◽  
Gang Cui ◽  
Feng Qin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Small Molecule ◽  
Memory Loss ◽  
Bioactive Natural Products ◽  
Drug Candidates ◽  
Ache Inhibitors ◽  
Cns Drugs ◽  
The Brain

<P>Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. Several hypotheses have been proposed for the pathogenesis based on the pathological changes in the brain of AD patients during the last few decades. Unfortunately, there is no effective agents/therapies to prevent or control AD at present. Currently, only a few drugs, which function as acetylcholinesterase (AChE) inhibitors or N-methyl-Daspartate (NMDA) receptor antagonists, are available to alleviate symptoms. </P><P> Since many small molecule natural products have shown their functions as agonists or antagonists of receptors, as well as inhibitors of enzymes and proteins in the brain during the development of central nervous system (CNS) drugs, it is likely that natural products will play an important role in anti-AD drug development. We review recent papers on using small molecule natural products as drug candidates for the treatment of AD. These natural products possess antioxidant, anti-inflammatory, anticholinesterase, anti-amyloidogenic and neuroprotective activities. Moreover, bioactive natural products intended to be used for preventing AD, reducing the symptoms of AD and the new targets for treatment of AD are summarized.</P>

Natural product-based nanomedicine: Recent advances and issues for the treatment of Alzheimer's disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Choy Ker Woon ◽  
Wong Kah Hui ◽  
Razif Abas ◽  
Muhammad Huzaimi Haron ◽  
Srijit Das ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Medicinal Plants ◽  
Drug Transport ◽  
The Elderly ◽  
Current Evidence ◽  
Alternative Approach ◽  
Progressive Neurodegeneration ◽  
The Brain

: Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and its severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano- sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material’s bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicine-based approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

MR Brain Screening using Optimization Techniques – A survey

2021 ◽  
Vol 17 ◽  
Author(s):  
Chitradevi D ◽  
Prabha S.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cell Loss ◽  
Optimization Techniques ◽  
Amyloid Β Protein ◽  
The Brain ◽  
Brain Tissues

Background: Alzheimer’s disease (AD) is associated with Dementia, and it is also a memory syndrome in the brain. It affects the brain tissues and causes major changes in day-to-day activities. Aging is a major cause of Alzheimer's disease. AD is characterized by two pathological hallmarks as, Amyloid β protein and neurofibrillary tangles of hyperphosphorylated tau protein. The imaging hallmarks for Alzheimer’s disease are namely, swelling, shrinkage of brain tissues due to cell loss, and atrophy in the brain due to protein dissemination. Based on the survey, 60% to 80% of dementia patients belong to Alzheimer’s disease. Introduction: AD is now becoming an increasing and important brain disease. The goal of AD pathology is to cause changes/damage in brain tissues. Alzheimer's disease is thought to begin 20 years or more before symptoms appear, with tiny changes in the brain that are undetectable to the person affected. The changes in a person's brain after a few years are noticeable through symptoms such as language difficulties and memory loss. Neurons in different parts of the brain have detected symptoms such as cognitive impairments and learning disabilities. In this case, neuroimaging tools are necessary to identify the development of pathology which relates to the clinical symptoms. Methods: Several approaches have been tried during the last two decades for brain screening to analyse AD with the process of pre-processing, segmentation and classification. Different individual such as Grey Wolf optimization, Lion Optimization, Ant Lion Optimization and so on. Similarly, hybrid optimization techniques are also attempted to segment the brain sub-regions which helps in identifying the bio-markers to analyse AD. Conclusion: This study discusses a review of neuroimaging technologies for diagnosing Alzheimer's disease, as well as the discovery of hallmarks for the disease and the methodologies for finding hallmarks from brain images to evaluate AD. According to the literature review, most of the techniques predicted higher accuracy (more than 90%), which is beneficial for assessing and screening neurodegenerative illness, particularly Alzheimer's disease.

scholarly journals Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4532 ◽  
Author(s):  
Sujin Kim ◽  
Hyunju Chung ◽  
Han Ngoc Mai ◽  
Yunkwon Nam ◽  
Soo Jung Shin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ionizing Radiation ◽  
Cognitive Deficits ◽  
Low Dose ◽  
Memory Loss ◽  
M2 Polarization ◽  
Phenotype Switching ◽  
5Xfad Mice ◽  
The Brain

Alzheimer’s disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aβ deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aβ pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aβ deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aβ accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aβ-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aβ deposition and memory loss.

scholarly journals IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

2016 ◽  
Vol 113 (19) ◽  
pp. E2705-E2713 ◽  
Author(s):  
Amy K. Y. Fu ◽  
Kwok-Wang Hung ◽  
Michael Y. F. Yuen ◽  
Xiaopu Zhou ◽  
Deejay S. Y. Mak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Innate Immune Response ◽  
Memory Loss ◽  
Neuronal Loss ◽  
Innate Immune ◽  
Therapeutic Role ◽  
Potential Therapeutic Role ◽  
The Brain

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

scholarly journals Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Davinelli ◽  
Nadia Sapere ◽  
Davide Zella ◽  
Renata Bracale ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protective Effects ◽  
Drug Candidates ◽  
Molecular Events ◽  
Therapeutic Value ◽  
Phytochemical Compounds ◽  
Multiple Levels ◽  
The Brain

Alzheimer’s disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

scholarly journals Alzheimer’s disease under the purview of Graph Theory Centric Genetic Networks

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yegnanarayanan Venkatraman ◽  
◽  
Narayanaa Y Krithicaa ◽  
Valentina E. Balas ◽  
Marius M. Balas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Graph Theory ◽  
Network Theory ◽  
Memory Loss ◽  
Amyloid Plaque ◽  
Brain Regions ◽  
Protein Protein Interaction ◽  
Communication Demands ◽  
The Brain

Notice that the synapsis of brain is a form of communication. As communication demands connectivity, it is not a surprise that "graph theory" is a fastest growing area of research in the life sciences. It attempts to explain the connections and communication between networks of neurons. Alzheimer’s disease (AD) progression in brain is due to a deposition and development of amyloid plaque and the loss of communication between nerve cells. Graph/network theory can provide incredible insights into the incorrect wiring leading to memory loss in a progressive manner. Network in AD is slanted towards investigating the intricate patterns of interconnections found in the pathogenesis of brain. Here, we see how the notions of graph/network theory can be prudently exploited to comprehend the Alzheimer’s disease. We begin with introducing concepts of graph/network theory as a model for specific genetic hubs of the brain regions and cellular signalling. We begin with a brief introduction of prevalence and causes of AD followed by outlining its genetic and signalling pathogenesis. We then present some of the network-applied outcome in assessing the disease-signalling interactions, signal transduction of protein-protein interaction, disturbed genetics and signalling pathways as compelling targets of pathogenesis of the disease.

scholarly journals Image processing for early detection of Alzheimer’s disease using Iridology

2020 ◽  
Vol 11 (4) ◽  
pp. 5555-5559
Author(s):  
Asuntha A ◽  
Sai Kalyan Reddy R ◽  
Vamshikrishna K ◽  
Premsagar N
Keyword(s):  
Alzheimer’S Disease ◽  
Image Processing ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Region Of Interest ◽  
Colour Pattern ◽  
Training Methods ◽  
Iris Image ◽  
Alternative Research ◽  
The Brain

Alzheimer's disease is caused by genetics, personal lifestyle and other environmental factors. It is an irreversible disease that slowly destroys the brain memory cells. There are no specific methods for the detection of Alzheimer's disease. The primary symptoms of Alzheimer's disease are memory loss, difficulty in thinking, a problem in writing and speaking and others. Iridology is alternative research that has gained more popularity in recent years, which studies the alterations of the iris in correspondence with the organs of the human body. The combination of digital image processing with Iridology gives an excellent opportunity to explore and learn about different neuronal diseases, specifically Alzheimer's disease. In this work, MATLAB software is applied to determine the colour, pattern and other factors that show the existence of Alzheimer's disease. The noise in the iris image is removed by the Gaussian filter, followed by histogram analyses and cropping. The Hough circle transform is used to identify the region of interest and to convert the circular iris image into rectangle form. In the training methods, the SVM and CNN classifiers are used to classify whether the person has Alzheimer's disease. Finally, the results are compared with the real-time images.

A Systematic Review on Donepezil-based Derivatives as Potential Cholinesterase Inhibitors for Alzheimer’s Disease

2019 ◽  
Vol 26 (30) ◽  
pp. 5625-5648 ◽  
Author(s):  
Jan Korabecny ◽  
Katarina Spilovska ◽  
Eva Mezeiova ◽  
Ondrej Benek ◽  
Radomir Juza ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Nmda Receptor Antagonist ◽  
Amyloid Burden ◽  
Ache Inhibitors ◽  
Intellectual Capacity ◽  
Β Amyloid

: Alzheimer’s Disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also through reduction of β-amyloid burden. This review presents the overview of donepezilrelated compounds as potential anti-AD drugs developed on the basis of cholinergic hypothesis to act as solely AChE and butyrylcholinesterase (BChE) inhibitors.

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