scholarly journals New Approaches to Treating Alzheimer's Disease

2015 ◽  
Vol 7 ◽  
pp. PMC.S13210 ◽  
Author(s):  
Hailin Zheng ◽  
Mati Fridkin ◽  
Moussa Youdim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Defense Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Network Medicine ◽  
Pathway Network ◽  
Drug Candidates ◽  
New Approaches ◽  
Single Target ◽  
Ad Therapy

To date, no truly efficacious drugs for Alzheimer's disease (AD) have been developed; moreover, all new anti-AD drugs developed since 2003 have failed. To succeed where previous ones have failed in drug development, new approaches for AD therapy are needed. Here we discuss the potential application of network medicine as a new approach to AD treatment. Unlike traditional approaches focused on a single target/pathway, network medicine targets and restores disease-disrupted networks through simultaneous modulation of numerous proteins (targets)/pathways involved in AD pathogenesis. We consider several drug candidates under development for AD therapy, including Keap1–Nrf2 regulators, endogenous neurogenic agents, and hypoxia-inducible factor 1 (HIF-1) activators. These drug candidates are multi-target ligands with the potential to further develop as network medicines, since they act as master regulators to initiate a broad range of cellular defense mechanisms/cytoprotective genes that exert their efficacy in a holistic way. We also explore their diverse mechanisms of action and potential disease-modifying effects, which may have profound implications for drug discovery.

The hybrid compounds as multi-target ligands for the treatment of Alzheimer's Disease: Considerations on Donepezil

2021 ◽  
Vol 21 ◽  
Author(s):  
Hayrettin Ozan Gulcan ◽  
Muberra Kosar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibition ◽  
Recent Period ◽  
Hybrid Molecule ◽  
Design Studies ◽  
Drug Candidates ◽  
Hybrid Molecules ◽  
Ad Therapy ◽  
Main Strategy

: The strategies to combat Alzheimer’s Disease (AD) have been changing with respect to the failures of many drug candidates assessed in clinical studies, the complex pathophysiology of AD, and the limitations of the current drugs employed. So far, none of the targets, either validated or nonvalidated, have been shown to be purely causative in the generation and development of AD. Considering the progressive and the neurodegenerative characteristics of the disease, the main strategy has been based on the design of molecules capable of showing activity on more than one receptor, and it is defined as multi-target ligand design strategy. The hybrid molecule concept is an outcome of this approach. Donepezil, as one of the currently employed drugs for AD therapy, has also been utilized in hybrid drug design studies. This review has aimed to present the promising donepezil-like hybrid molecules introduced in the recent period. Particularly, multi-target ligands with additional activities concomitant to cholinesterase inhibition are preferred.

Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease

2021 ◽  
Vol 28 ◽  
Author(s):  
Bhupinder Kumar ◽  
Amandeep Thakur ◽  
Ashish Ranjan Dwivedi ◽  
Rakesh Kumar ◽  
Vinod Kumar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Strategies ◽  
Design Strategies ◽  
Drug Candidates ◽  
Esterase Inhibitors ◽  
Current Review ◽  
Single Target ◽  
Symptomatic Management ◽  
Β Amyloid

Abstract: Alzheimer’s disease (AD) is a complex neurological disorder, and multiple pathological factors are believed to be involved in the genesis and progression of the disease. A number of hypotheses, including Acetylcholinesterase, Monoamine oxidase, β-Amyloid, Tau protein, etc., have been proposed for the initiation and progression of the disease. At present, acetylcholine esterase inhibitors and memantine (NMDAR antagonist) are the only approved therapies for the symptomatic management of AD. Most of these single-target drugs have miserably failed in the treatment or halting the progression of the disease. Multi-factorial diseases like AD require complex treatment strategies that involve simultaneous modulation of a network of interacting targets. Since the last few years, Multi-Target-Directed Ligands (MTDLs) strategy, drugs that can simultaneously hit multiple targets, is being explored as an effective therapeutic approach for the treatment of AD. In the current review article, the authors have briefly described various pathogenic pathways associated with AD. The importance of Multi-Target-Directed Ligands and their design strategies in recently reported articles have been discussed in detail. Potent leads are identified through various structure-activity relationship studies, and their drug-like characteristics are described. Recently developed promising compounds have been summarized in the article. Some of these MTDLs with balanced activity profiles against different targets have the potential to be developed as drug candidates for the treatment of AD.

The use of Huperzia species for the treatment of Alzheimer’s disease

2019 ◽  
Vol 31 (3) ◽  
Author(s):  
Dang Kim Thu ◽  
Dao Thi Vui ◽  
Nguyen Thi Ngoc Huyen ◽  
Duong Ky Duyen ◽  
Bui Thanh Tung
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medicinal Plants ◽  
Adverse Reactions ◽  
Memory Loss ◽  
Neural System ◽  
Drug Candidates ◽  
Potential Source ◽  
Pubmed Database ◽  
Ad Therapy

AbstractAlzheimer’s disease (AD), which relates to nervous degeneration, is the most popular form of memory loss. The pathogenesis of AD is not fully understood, and there are no therapies for this disorder. Some drugs have been used in clinical applications for preventing and treating AD, but they have significant adverse reactions. Therefore, there is a need to develop treatment for AD. Traditional medicine has used many medicinal plants to alleviate the symptoms of AD. Medicinal plants may reduce neurodegenerative disorders with fewer side effects than chemical drugs, and they are promising drug candidates for AD therapy. This review is the summary of the pathogenesis and treatments of AD and includes information about the chemistry and bioactivities of some medicinal plants from the Huperzia species, such as Huperzia saururus, Huperzia selago, Huperzia phlegmaria, Huperzia fargesii, Huperzia serrata, Huperzia reflexa and Huperzia quadrifariata, that are used for the treatment of AD. We searched literature, including Medline, Embase, Google Scholar and PubMed database, and did a bibliographic review of relevant articles. Key words included Huperzia species, huperzine, huperin, Huperzia and Alzheimer’s disease. We found that the main bioactive compounds of the Huperzia species are alkaloids, which have shown significant effects on preventing the development of AD. They are new promising compounds against AD due to their antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities in the neural system. Our conclusion from this review is that the Huperzia species are potential source containing various pharmaceutical compounds for the treatment of AD.

Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials

2020 ◽  
Vol 13 (4) ◽  
pp. 273-294 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Javad Amini ◽  
Nima Sanadgol ◽  
Gholamhassan Vaezi ◽  
Kazem Parivar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Trial Design ◽  
Treatment Approaches ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Approved Drugs ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated. Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators. Methods: We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia” and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that met the objective of this study were included for further evaluations. Results: Drug candidates have been categorized into two main groups including antibodies, peptides or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra, and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol, Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine, Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole) and frequently ameliorate cognitive dysfunctions. Conclusion: The presences of a small number of candidates in the last phase suggest that a large number of candidates have had an undesirable side effect or were unable to pass essential eligibility for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand, and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating disease in the near future.

scholarly journals Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Sirui Guo ◽  
Jiahong Wang ◽  
Huarong Xu ◽  
Weiwei Rong ◽  
Cheng Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Protein Signaling ◽  
Pi3k Inhibitor Ly294002 ◽  
Single Target ◽  
Biological Methods ◽  
Cognition Impairment ◽  
First Time

Alzheimer’s disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aβ25-35 and D-gal-induced AD rats and Aβ25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aβ25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

scholarly journals Exploitation of Marine Molecules to Manage Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 373
Author(s):  
Marisa Silva ◽  
Paula Seijas ◽  
Paz Otero
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Nmda Receptor Antagonists ◽  
Average Life ◽  
Average Life Expectancy ◽  
Large Reservoir ◽  
Drug Candidates ◽  
Neurodegenerative Process ◽  
Main Action

Neurodegenerative diseases are sociosanitary challenges of today, as a result of increased average life expectancy, with Alzheimer’s disease being one of the most prevalent. This pathology is characterized by brain impairment linked to a neurodegenerative process culminating in cognitive decline and behavioral disorders. Though the etiology of this pathology is still unknown, it is usually associated with the appearance of senile plaques and neurofibrillary tangles. The most used prophylaxis relies on anticholinesterase drugs and NMDA receptor antagonists, whose main action is to relieve symptoms and not to treat or prevent the disease. Currently, the scientific community is gathering efforts to disclose new natural compounds effective against Alzheimer’s disease and other neurodegenerative pathologies. Marine natural products have been shown to be promising candidates, and some have been proven to exert a high neuroprotection effect, constituting a large reservoir of potential drugs and nutraceutical agents. The present article attempts to describe the processes of extraction and isolation of bioactive compounds derived from sponges, algae, marine bacteria, invertebrates, crustaceans, and tunicates as drug candidates against AD, with a focus on the success of pharmacological activity in the process of finding new and effective drug compounds.

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

scholarly journals Potential New Approaches for Diagnosis of Alzheimer's Disease and Related Dementias

2020 ◽  
Vol 11 ◽  
Author(s):  
R. Scott Turner ◽  
Terry Stubbs ◽  
Don A. Davies ◽  
Benedict C. Albensi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
New Approaches
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