scholarly journals Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3233 ◽  
Author(s):  
Syed Sayeed Ahmad ◽  
Haroon Khan ◽  
Syed Mohd. Danish Rizvi ◽  
Siddique Akber Ansari ◽  
Riaz Ullah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Computational Study ◽  
Senile Plaques ◽  
Natural Compounds ◽  
Positive Control ◽  
Aβ Peptide ◽  
Protein Protein Interaction ◽  
Lead Compounds ◽  
Glycation End Products

Alzheimer’s disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aβ) peptides in senile plaques. The interaction of Aβ and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aβ into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aβ peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aβ peptide–compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aβ and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aβ and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer’s disease treatment.

scholarly journals A Comparative Study on 5hmC Targeting Regulation of Neurons in AD Mice by Several Natural Compounds

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Dongyi Cao ◽  
Dewei Jiang ◽  
Dongming Zhou ◽  
Hong Yu ◽  
Jiali Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein A ◽  
Natural Compounds ◽  
Positive Control ◽  
Positive Influence ◽  
Dot Blot ◽  
Dendritic Branches ◽  
And Control ◽  
The Brain

A series of studies have confirmed that DNA methylation disorder (5mC/5hmC) is closely related to the occurrence and development of some diseases, such as Alzheimer’s disease (AD). This study aims at discovering natural compounds that could adjust and control 5-hydroxymethylcytosine (5hmC) levels and improve Alzheimer’s disease (AD) neuronal status. Cordycepin and cordycepic acid were selected as research materials, with resveratrol as positive control. The results of Dot Blot indicated that cordycepin, cordycepic acid, and resveratrol significantly increased the expression level of 5hmC. Combined with qPCR results, it was revealed that cordycepin increased the expression of ten-eleven translocation (TETs) mRNA compared with the abovementioned cordycepic acid and resveratrol. Besides, cordycepin dramatically reduced the transcription level of Apolipoprotein E (ApoE), suggesting that cordycepin might hinder the formation of NFTs (neurofibrillary tangles) and the accumulation of amyloid β-protein (Aβ) in the brain by reducing the expression of ApoE, resulting in affecting the progression of AD. Meanwhile, the immunofluorescence (IF) staining results demonstrated that the percentage of differentiation of SHSY-5Y cells reasonably increased after the treatment of cordycepin and cordycepic acid. Simultaneously, the length of axons and the number of dendritic branches in mouse primary neurons were substantially increased by cordycepin. The screening results illustrated that cordycepin had a positive influence on the level of 5hmC and the morphology of neurons, and most of the effects were better compared to the positive control (resveratrol). It indicated that cordycepin delayed the progression of neurodegenerative diseases such as AD. However, the specific mechanism of action still needs to be further investigated. Our research provided a foundation for further discussion about the influence of cordycepin on AD and a new idea for the pathological study of related diseases.

scholarly journals Tau aggregates possibly compromise neuronal health in the C. elegans model of Alzheimer’s disease

2020 ◽  
Vol 1 (6) ◽  
pp. 46-48
Author(s):  
Sanjib Guha ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Intercellular Space ◽  
Senile Plaques ◽  
Aβ Peptide ◽  
Progressive Decline ◽  
C Elegans ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the most common degenerative brain disease in the aged population [1]. By 2050, AD prevalence is expected to increase from 4.7 million (based on 2010 census) to 13.8 million people [2]. It is characterized by the progressive decline of cognition and memory, as well as changes in behavior and personality [1]. Pathological hallmarks of AD include mainly formation of senile plaques consisting of amyloid-beta (Aβ) peptide in the intercellular space and neurofibrillary tangles (NFTs) in the cell bodies, which are primarily composed of abnormally modified tau protein [3].

PYRAZOLINE CONTAINING MOLECULES AS MULTIFUNCTIONAL AGENTS IN ALZHEIMER’S DISEASE

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (10) ◽  
pp. 22-25
Author(s):  
M Khambete ◽  
P. Murumkar ◽  
A Kumar ◽  
T. Darreh-Shori ◽  
S. De ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
The Past ◽  
Glycation End Products ◽  
Aβ Aggregation ◽  
Aggregation Inhibition ◽  
Multifunctional Agents ◽  
Β Amyloid ◽  
Multifunctional Molecules

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease which is caused mainly due to accumulation of an aberrant protein known as β-amyloid in the form of senile plaques. However, over the past few years, network biology studies have indicated that classical “one drug-one target” hypothesis may not work in diseases such as AD where the biochemical disease mechanisms are intricately interconnected. therefore, multifunctional molecules which can modulate several targets could be the key towards finding the therapeutics for this debilitating disorder. Keeping this in mind, several pyrazoline containing molecules with promising Aβ aggregation inhibition potential were explored further against key targets involved in AD, such as cholinesterases, oxidative stress and advanced glycation end products (AGe). Some potential multifunctional molecules were identified as a result of this work.

Synaptic Mitochondria: An Early Target of Amyloid-β and Tau in Alzheimer’s Disease

2021 ◽  
pp. 1-24
Author(s):  
Angie K. Torres ◽  
Claudia Jara ◽  
Han S. Park-Kang ◽  
Catalina M. Polanco ◽  
Diego Tapia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurofibrillary Tangles ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Aβ Peptide ◽  
Predisposing Factor ◽  
Age Related ◽  
Synaptic Mitochondria

Alzheimer’s disease (AD) is characterized by cognitive impairment and the presence of neurofibrillary tangles and senile plaques in the brain. Neurofibrillary tangles are composed of hyperphosphorylated tau, while senile plaques are formed by amyloid-β (Aβ) peptide. The amyloid hypothesis proposes that Aβ accumulation is primarily responsible for the neurotoxicity in AD. Multiple Aβ-mediated toxicity mechanisms have been proposed including mitochondrial dysfunction. However, it is unclear if it precedes Aβ accumulation or if is a consequence of it. Aβ promotes mitochondrial failure. However, AβPP could be cleaved in the mitochondria producing Aβ peptide. Mitochondrial-produced Aβ could interact with newly formed ones or with Aβ that enter the mitochondria, which may induce its oligomerization and contribute to further mitochondrial alterations, resulting in a vicious cycle. Another explanation for AD is the tau hypothesis, in which modified tau trigger toxic effects in neurons. Tau induces mitochondrial dysfunction by indirect and apparently by direct mechanisms. In neurons mitochondria are classified as non-synaptic or synaptic according to their localization, where synaptic mitochondrial function is fundamental supporting neurotransmission and hippocampal memory formation. Here, we focus on synaptic mitochondria as a primary target for Aβ toxicity and/or formation, generating toxicity at the synapse and contributing to synaptic and memory impairment in AD. We also hypothesize that phospho-tau accumulates in mitochondria and triggers dysfunction. Finally, we discuss that synaptic mitochondrial dysfunction occur in aging and correlates with age-related memory loss. Therefore, synaptic mitochondrial dysfunction could be a predisposing factor for AD or an early marker of its onset.

A Computational Study of Natural Compounds from Bacopa monnieri in the Treatment of Alzheimer's Disease

2020 ◽  
Vol 26 (7) ◽  
pp. 790-800
Author(s):  
Qazi M.S. Jamal ◽  
Mughees U. Siddiqui ◽  
Ali H. Alharbi ◽  
Fahad Albejaidi ◽  
Salman Akhtar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrophobic Interactions ◽  
Computational Study ◽  
Treatment Options ◽  
Natural Compounds ◽  
Bacopa Monnieri ◽  
The Public ◽  
Health Related ◽  
Inhibition Constants

: Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence and progression indicate the needs for best treatment options. The present bioinformatics study explores the binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a significant role in finding out the interacting position at the active site. However, after analyzing the binding energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of inhibitors.

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Therapeutic Properties of Several Chemical Compounds from Salvia officinalis L. in Alzheimer’s Disease

2020 ◽  
Vol 21 ◽  
Author(s):  
Georgiana Uță ◽  
Denisa Ștefania Manolescu ◽  
Speranța Avram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Chemical Compounds ◽  
Natural Compounds ◽  
Salvia Officinalis ◽  
Chemical Structures ◽  
In Silico Studies ◽  
Wide Range ◽  
Salvia Officinalis L

Background.: Currently, the pharmacological management in Alzheimer's disease is based on several chemical structures, represented by acetylcholinesterase and N-methyl-D-aspartate (NMDA) receptor ligands, with still unclear molecular mechanisms, but severe side effects. For this reason, a challenge for Alzheimer's disease treatment remains to identify new drugs with reduced side effects. Recently, the natural compounds, in particular certain chemical compounds identified in the essential oil of peppermint, sage, grapes, sea buckthorn, have increased interest as possible therapeutics. Objectives.: In this paper, we have summarized data from the recent literature, on several chemical compounds extracted from Salvia officinalis L., with therapeutic potential in Alzheimer's disease. Methods.: In addition to the wide range of experimental methods performed in vivo and in vitro, also we presented some in silico studies of medicinal compounds. Results. Through this mini-review, we present the latest information regarding the therapeutic characteristics of natural compounds isolated from Salvia officinalis L. in Alzheimer's disease. Conclusion.: Thus, based on the information presented, we can say that phytotherapy is a reliable therapeutic method in a neurodegenerative disease.

Biological Signatures of Alzheimer’s Disease

2020 ◽  
Vol 20 (9) ◽  
pp. 770-781 ◽  
Author(s):  
Poornima Sharma ◽  
Anjali Sharma ◽  
Faizana Fayaz ◽  
Sharad Wakode ◽  
Faheem H. Pottoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Senile Plaque ◽  
Senile Plaques ◽  
Amyloid Deposition ◽  
Immune Defense ◽  
Amyloid Angiopathy ◽  
Microvascular Changes ◽  
Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

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