scholarly journals Drug Repurposing for Alzheimer’s Disease based on Protein-Protein Interaction Network

2021 ◽  
Author(s):  
Negar Sadat Soleimani Zakeri ◽  
Saeid Pashazadeh ◽  
Habib MotieGhader
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Neurodegenerative Disorder ◽  
Gentian Violet ◽  
Interaction Network ◽  
New Drugs ◽  
Bipartite Network ◽  
Medical Studies ◽  
Gene Complexes

Abstract Background: Alzheimer's disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment is vital. This study proposes a method to extract substantial gene complexes and accomplish an enrichment analysis to introduce the most significant biological procedures. The next step is extracting the drugs related to AD and introduce some new drugs which may be useful for this disease. Results: To this end, protein-protein interactions (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. The next step was to construct a five bipartite network representing the genes of each group and their target miRNAs. Finally, a complete network including all the genes related to each gene complex group and genes’ target drug was illustrated. medical studies and publications were analyzed thoroughly to introduce AD-related drugs. Conclusions: This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. RALOXIFENE, GENTIAN VIOLET are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. These two drugs.

scholarly journals Drug Repurposing for Alzheimer’s Disease Based on Protein-Protein Interaction Network

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Negar Sadat Soleimani Zakeri ◽  
Saeid Pashazadeh ◽  
Habib MotieGhader
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interaction ◽  
Target Genes ◽  
Neurodegenerative Disorder ◽  
Gentian Violet ◽  
New Drugs ◽  
Medical Studies ◽  
Protein Protein Interaction ◽  
Gene Complexes

Alzheimer’s disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment are vital. This study proposes a method to extract substantial gene complexes and then introduces potential drugs in Alzheimer’s disease. To this end, a protein-protein interaction (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. An enrichment analysis to introduce the most important biological processes and pathways was accomplished on the obtained genes. The next step is extracting the drugs related to AD and introducing some new drugs which may be helpful for this disease. Finally, a complete network including all the genes associated with each gene complex group and genes’ target drug was illustrated. For validating the proposed potential drugs, Connectivity Map (CMAP) analysis was accomplished to determine target genes that are up- or downregulated by proposed drugs. Medical studies and publications were analyzed thoroughly to introduce AD-related drugs. This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. Raloxifene and gentian violet are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. Besides the primary goal, five bipartite networks representing the genes of each group and their target miRNAs were constructed to introduce target miRNAs.

scholarly journals Association and Gene–-Gene Interactions Study of Late-Onset Alzheimer’s Disease in the Russian Population

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1647
Author(s):  
Anna Bocharova ◽  
Kseniya Vagaitseva ◽  
Andrey Marusin ◽  
Natalia Zhukova ◽  
Irina Zhukova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Factor Model ◽  
Late Onset ◽  
Interaction Network ◽  
Russian Population ◽  
Protein Protein Interaction ◽  
Protective Haplotype ◽  
Single Snps

Alzheimer’s disease (AD) is a neurodegenerative disorder, and represents the most common cause of dementia. In this study, we performed several different analyses to detect loci involved in development of the late onset AD in the Russian population. DNA samples from 472 unrelated subjects were genotyped for 63 SNPs using iPLEX Assay and real-time PCR. We identified five genetic loci that were significantly associated with LOAD risk for the Russian population (TOMM40 rs2075650, APOE rs429358 and rs769449, NECTIN rs6857, APOE ε4). The results of the analysis based on comparison of the haplotype frequencies showed two risk haplotypes and one protective haplotype. The GMDR analysis demonstrated three significant models as a result: a one-factor, a two-factor and a three-factor model. A protein–protein interaction network with three subnetworks was formed for the 24 proteins. Eight proteins with a large number of interactions are identified: APOE, SORL1, APOC1, CD33, CLU, TOMM40, CNTNAP2 and CACNA1C. The present study confirms the importance of the APOE-TOMM40 locus as the main risk locus of development and progress of LOAD in the Russian population. Association analysis and bioinformatics approaches detected interactions both at the association level of single SNPs and at the level of genes and proteins.

scholarly journals Naturally Inspired Pyrimidines Analogues for Alzheimer’s Disease

2020 ◽  
Vol 19 (2) ◽  
pp. 136-151
Author(s):  
Shivani Singh ◽  
Meenakshi Dhanawat ◽  
Sumeet Gupta ◽  
Deepak Kumar ◽  
Saloni Kakkar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Multicomponent Reactions ◽  
Neurodegenerative Disorder ◽  
The Body ◽  
New Drugs ◽  
Atom Economy ◽  
Step Process ◽  
One Step ◽  
Made In

: Alzheimer’s disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.

scholarly journals The impact of anorexigenic peptides in experimental models of Alzheimer’s disease pathology

2019 ◽  
Vol 240 (2) ◽  
pp. R47-R72 ◽  
Author(s):  
Lenka Maletínská ◽  
Andrea Popelová ◽  
Blanka Železná ◽  
Michal Bencze ◽  
Jaroslav Kuneš
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Energy Homeostasis ◽  
Neurodegenerative Disorder ◽  
Experimental Studies ◽  
The Elderly ◽  
Experimental Models ◽  
New Drugs ◽  
Neuroprotective Effects ◽  
The Impact

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.

scholarly journals Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5582
Author(s):  
Alfred Ngenge Tamfu ◽  
Selcuk Kucukaydin ◽  
Balakyz Yeskaliyeva ◽  
Mehmet Ozturk ◽  
Rodica Mihaela Dinica
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
High Efficiency ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
New Drugs ◽  
Cholinesterase Inhibition ◽  
Natural Sources ◽  
Long Term Treatment

Alzheimer’s disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient’s daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aβ) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer’s disease.

scholarly journals Utility of animal models of Alzheimer’s disease in food bioactive research

2021 ◽  
Vol 13 ◽  
Author(s):  
Klaus W. Lange
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Clinical Success ◽  
Treatment Strategies ◽  
New Drugs ◽  
Preclinical Research ◽  
Novel Treatment Strategies

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by globally impaired cognition. AD research in animals has shown a substantial deficit in translational relevance. The most extensively used transgenic mouse models overexpress human genes associated with rare familial early-onset AD, which results in the formation of amyloid plaques. However, the most common form of AD (late-onset sporadic AD) is a multifactorial disorder involving different cytotoxic factors, including neurofibrillary pathology. Transgenic mice studies have been valuable in elucidating pathogenetic mechanisms that may be relevant to human AD. However, their utility in the development of novel treatment strategies and as preclinical testbeds of new drugs has been unsatisfactory. Animal models have so far failed to demonstrate predictive value in regard to novel therapies of AD, including the use of bioactive food components. While many therapeutic approaches assessed in animals have shown promising results, attempts to translate these findings to people with AD have been disappointing. Food scientists should be aware that the available animal models appear to be unable to predict clinical success in humans. Therefore, food bioactive research should focus on human-centric preventive approaches to AD in clinically meaningful settings rather than on highly questionable preclinical research in animals.

Synthesis and Cholinesterase Inhibitory Activity of N-Phosphorylated/ N-Tiophosphorylated Tacrine

2020 ◽  
Vol 16 (7) ◽  
pp. 947-957
Author(s):  
Maja Przybyłowska ◽  
Iwona Inkielewicz-Stepniak ◽  
Szymon Kowalski ◽  
Krystyna Dzierzbicka ◽  
Sebastian Demkowicz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sodium Iodide ◽  
31P Nmr ◽  
Neurodegenerative Disorder ◽  
Docking Studies ◽  
New Drugs ◽  
Binding Ability ◽  
Electric Eel ◽  
Cholinesterase Inhibitory Activity

Background: Alzheimer’s disease (AD) is progressive and irreversible neurodegenerative disorder. Current pharmacotherapy is not able to stop progression of the disease and can only improve cognitive functions. Therefore, new drugs are being sought that will slow down the development of the disease. Objective: Novel phosphorus and thiophosphorus tacrine derivatives 7-14 were designed, synthesized and their biological activity and molecular modeling was investigated as a new potential anti- Alzheimer’s disease (AD) agents. Methods: 9-Chlorotacrine was treated with propane-1,3-diamine in the presence of sodium iodide to yield N1-(1,2,3,4-tetrahydroacridin-9-yl)propane-1,3-diamine 6. Finally, it was treated with corresponding acid ester or thioester to give phosphorus or thiophosphorus tacrine derivative 7-14. All of the obtained final structures were characterized by 1H NMR, 13C NMR, 31P NMR and MS. Results: The results of the docking studies showed that the newly designed phosphorus and thiophosphorus tacrine analogs, theoretically possess AChE and BChE-binding ability. Kinetic study showed that 8 and 12 in the series proved to be more potent electric eel AChE (eeAChE) and human (hAChE) inhibitors than tacrine, where 8 inhibited eeAChE three times more than the referenced drug. The highest BChE inhibition revealed 11 and 13. The most active compounds against eeAChE, hAChE and BChE showed mixed type of inhibition. Conclusion: All new synthesized compound exhibited lower toxicity against neuroblastoma.cell line (SH-SY5Y) in comparison with tacrine. Two analogues in the series, 7 and 9, demonstrated lack of cytotoxicity against hepatocellular cells (hepG2).

scholarly journals Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach

2019 ◽  
Vol 17 (4) ◽  
pp. 352-365 ◽  
Author(s):  
Puneet Talwar ◽  
Renu Gupta ◽  
Suman Kushwaha ◽  
Rachna Agarwal ◽  
Luciano Saso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Systems Biology ◽  
Candidate Genes ◽  
Protein Interactions ◽  
Interaction Network ◽  
Potential Drug ◽  
Human Herpes Virus 8 ◽  
Drug Candidates

Alzheimer’s disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score≥0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug- Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein– Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates.

A Systematic Review on the Role of Natural Products in Modulating the Pathways in Alzheimer’s Disease

2017 ◽  
Vol 87 (1-2) ◽  
pp. 99-116 ◽  
Author(s):  
Sandip T. Auti ◽  
Yogesh A. Kulkarni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Conventional Medicine ◽  
Neuronal Cell ◽  
Specific Effect ◽  
New Drugs ◽  
Disease Pathways

Abstract. Alzheimer’s disease (AD) is the most common neurodegenerative disorder to date, with no cure or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles in brain. Despite extensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look for alternative therapies and new drugs. Use of natural products in medicine has gained popularity in recent years and several natural compounds with neuroprotective effects have been studied in detail. Some of them target the disease pathways and improve cognition by directly affecting amyloidogenesis, programmed cell death and increase neuronal cell survival. Currently, phytochemicals like polyphenols, alkaloids, terpenes, flavonoids, tannins, saponins and vitamins from plants have received a special attention from the scientific community against the pathological processes in conditions like cancer, cardiovascular diseases and neurodegenerative diseases. Many efforts have been made to unravel the molecular mechanisms and the specific interactions of phytochemicals, which targets disease pathways in the AD. Further studies on these natural products and their mechanism of action, target specific effect in disease pathology parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine in treatment of AD. This review presents detailed information on natural products like polyphenols, alkaloids and terpenes with their potential effects in Alzheimer’s disease.

scholarly journals Management of the predementia stage of Alzheimer’s disease, complicated with hypoactive delirium

2021 ◽  
Vol 25 (6) ◽  
pp. 40-46
Author(s):  
O. N. Tkacheva ◽  
M. A. Cherdak ◽  
E. A. Mkhitaryan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Clinical Laboratory ◽  
Neurodegenerative Disorder ◽  
Cognitive Status ◽  
New Drugs ◽  
Antidementia Drugs ◽  
Diagnostic Approaches ◽  
Hypoactive Delirium

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly population leading to the development of dementia. The emergence of modern diagnostic approaches makes possible reveal AD at predementia stage and study new drugs with pathogenetic and neuroprotective properties before severe cognitive impairment (dementia) arises. We present a description of patient with amnestic type of mild cognitive impairment with subsequent follow-up for more than two years. AD presence in mentioned patient was confirmed by evaluation of specific clinical, laboratory and instrumental biomarkers. Therapy with akatinol memantine (one of the main antidementia drugs in AD) at dose 20 mg/day was accompanied by cognitive defect stabilization. After two years of therapy acute severe decompensation related to hypoactive delirium due to respiratory infection was observed, which was followed by marked cognitive status deterioration. Daily dose of akatinol memantine was increased to 30 mg with subsequent restoration of baseline cognitive status. Possible mechanisms of akatinol memantine action and its effects in management of geriatric patients with AD including role in delirium therapy are discussed.

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