Scutellaria barbata Leaf Extract Mediated Gold Nanoparticles for Alzheimer’s Disease Treatment by Metal-Induced Amyloid β Aggregation Inhibition

2019 ◽  
Vol 31 (6) ◽  
pp. 1269-1273
Author(s):  
Guoqing Wang ◽  
Jingcun Dai ◽  
Xinjian Lu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gold Nanoparticles ◽  
Leaf Extract ◽  
Amyloid Β ◽  
Disease Treatment ◽  
Scutellaria Barbata ◽  
Aggregation Inhibition

scholarly journals Immunotherapeutic Strategies for Alzheimer's Disease Treatment

2009 ◽  
Vol 9 ◽  
pp. 909-919 ◽  
Author(s):  
Beka Solomon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Passive Immunization ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Treatment ◽  
Naturally Occurring ◽  
Age Related ◽  
The Central Nervous System ◽  
Naturally Occurring Antibodies

Naturally occurring antibodies against amyloid-β peptides have been found in human cerebrospinal fluid and in the plasma of healthy individuals, but were significantly lower in Alzheimer's disease (AD) patients, suggesting that AD may be an immunodeficient disorder. The performance of anti-amyloid-β antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system, preventing and dissolving amyloid-β plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Active and/or passive immunization against the amyloid-β peptide has been proposed as a method for preventing and/or treating AD. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.

Insights into the Drug Repositioning Applied to the Alzheimer's Disease Treatment and Future Perspectives

2018 ◽  
Vol 15 (12) ◽  
pp. 1161-1178 ◽  
Author(s):  
Alexandre A. de Castro ◽  
Elaine F.F. da Cunha ◽  
Ander F. Pereira ◽  
Flavia V. Soares ◽  
Daniel H.S. Leal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Late Onset ◽  
Drug Repositioning ◽  
Amyloid Β ◽  
Disease Treatment ◽  
Beneficial Effects ◽  
Relevant Evidence ◽  
Treatment Conditions

Introduction: Alzheimer's disease is known to be a chronic disease, with an estimated prevalence of about 10-30%, considering the population over 60 years of age. Most patients with this disorder (> 95%) present the sporadic form, being characterized by a late onset (80-90 years of age), and it is the consequence of the failure to clear the amyloid-β (Aβ) peptide from the interstices of the brain. Significant numbers of genetic risk factors for the sporadic disease have been researched. Some existing drugs for Alzheimer's disease provide symptomatic benefit for up to 12 months, but there are no approved disease- modifying therapies. In this line, a complementary strategy based on repositioning drugs which are approved for the treatment of other disorders could be interesting. It is noteworthy the fact that some clinical trials indicate that several classes of drugs own potent and beneficial effects on the Alzheimer's disease treatment. In this present work, we present the details and evaluation of these alternative treatments. It has highlighted several compounds with relevant evidence for this purpose, which deserves further investigation to clarify optimal treatment conditions in the clinical trials of patients with Alzheimer's disease.

Critical Review of the Alzheimer’s Disease Non-Transgenic Models: Can They Contribute to Disease Treatment?

2020 ◽  
pp. 1-24
Author(s):  
Julio A. Flores-Cuadra ◽  
Alanna Madrid ◽  
Patricia L. Fernández ◽  
Ambar R. Pérez-Lao ◽  
Diana C. Oviedo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Critical Review ◽  
Amyloid Β ◽  
Therapeutic Strategies ◽  
Intervention Strategies ◽  
Transgenic Models ◽  
Preclinical Research ◽  
Disease Treatment

Alzheimer’s disease (AD) is a growing neurodegenerative disease without effective treatments or therapies. Despite the use of different approaches and an extensive variety of genetic amyloid based models, therapeutic strategies remain elusive. AD is characterized by three main pathological hallmarks that include amyloid-β plaques, neurofibrillary tangles, and neuroinflammatory processes; however, many other pathological mechanisms have been described in the literature. Nonetheless, the study of the disease and the screening of potential therapies is heavily weighted toward the study of amyloid-β transgenic models. Non-transgenic models may aid in the study of complex pathological states and provide a suitable complementary alternative to evaluating therapeutic biomedical and intervention strategies. In this review, we evaluate the literature on non-transgenic alternatives, focusing on the use of these models for testing therapeutic strategies, and assess their contribution to understanding AD. This review aims to underscore the need for a shift in preclinical research on intervention strategies for AD from amyloid-based to alternative, complementary non-amyloid approaches.

Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease

2019 ◽  
Vol 16 (9) ◽  
pp. 772-800 ◽  
Author(s):  
Eva Mezeiova ◽  
Katarina Chalupova ◽  
Eugenie Nepovimova ◽  
Lukas Gorecki ◽  
Lukas Prchal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitor ◽  
Amyloid Β ◽  
Direct Interaction ◽  
Extensive Literature ◽  
Aβ Aggregation ◽  
Aggregation Inhibition ◽  
Approved Drugs

: Alzheimer's Disease (AD) is a neurodegenerative disorder with an increasing impact on society. Because currently available therapy has only a short-term effect, a huge number of novel compounds are developed every year exploiting knowledge of the various aspects of AD pathophysiology. To better address the pathological complexity of AD, one of the most extensively pursued strategies by medicinal chemists is based on Multi-target-directed Ligands (MTDLs). Donepezil is one of the currently approved drugs for AD therapy acting as an acetylcholinesterase inhibitor. In this review, we have made an extensive literature survey focusing on donepezil-derived MTDL hybrids primarily targeting on different levels cholinesterases and amyloid beta (Aβ) peptide. The targeting includes direct interaction of the compounds with Aβ, AChE-induced Aβ aggregation, inhibition of BACE-1 enzyme, and modulation of biometal balance thus impeding Aβ assembly.

scholarly journals Novel Donepezil–Arylsulfonamide Hybrids as Multitarget-Directed Ligands for Potential Treatment of Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1658
Author(s):  
Fausto Queda ◽  
Sonia Calò ◽  
Karolina Gwizdala ◽  
João D. Magalhães ◽  
Sandra M. Cardoso ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Ache Inhibitor ◽  
Target Drug ◽  
Aβ Aggregation ◽  
Aggregation Inhibition ◽  
Inhibitor Drug ◽  
A Current

Alzheimer’s disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD therapies. Herein, a series of hybrid compounds are reported which were designed and developed by combining an aryl-sulfonamide function with a benzyl-piperidine moiety, the pharmacophore of donepezil (a current anti-AD acetylcholinesterase AChE inhibitor drug) or its benzyl-piperazine analogue. The in vitro results indicate that some of these hybrids achieve optimized activity towards two main AD targets, by displaying excellent AChE inhibitory potencies, as well as the capability to prevent amyloid-β (Aβ) aggregation. Some of these hybrids also prevented Aβ-induced cell toxicity. Significantly, drug-like properties were predicted, including for blood-brain permeability. Compound 9 emerged as a promising multi-target lead compound (AChE inhibition (IC50 1.6 μM); Aβ aggregation inhibition 60.7%). Overall, this family of hybrids is worthy of further exploration, due to the wide biological activity of sulfonamides.

scholarly journals Amyloid-β precursor protein synthesis inhibitors for Alzheimer's disease treatment

2014 ◽  
Vol 76 (4) ◽  
pp. 629-630 ◽  
Author(s):  
Nigel H. Greig ◽  
Kumar Sambamurti ◽  
Debomoy K. Lahiri ◽  
Robert E. Becker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Synthesis ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Protein Synthesis Inhibitors ◽  
Disease Treatment

Anti-Amyloid Aggregating Gold Nanoparticles: Can they Really be Translated from Bench to Bedside for Alzheimer's Disease Treatment?

2020 ◽  
Vol 21 (12) ◽  
pp. 1184-1192
Author(s):  
Sibhghatulla Shaikh ◽  
Nazia Nazam ◽  
Syed Mohd Danish Rizvi ◽  
Talib Hussain ◽  
Aisha Farhana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gold Nanoparticles ◽  
Treatment Strategy ◽  
Amyloid Β ◽  
Therapeutic Agents ◽  
Current Status ◽  
Amyloid Β Protein ◽  
Appropriate Treatment ◽  
Β Protein

: Alzheimer’s disease (AD) is characterized by deposition of amyloid-β protein aggregates and an appropriate treatment strategy is urgently needed, as the number of diagnosed cases continues to increase. The management of AD and other brain-associated diseases is limited by the blood brain barrier and its selective control of drug passage. In fact, most of the promising drugs have restricted curative effects on AD owing to their lower bioavailability. Gold nanoparticles (AuNPs) have emerged as attractive therapeutic agents and have distinctive properties that could contribute to the development of a novel treatment strategy for neurodegenerative disorders. In this review article, we attempt to identify promising ways of developing competent AD therapeutic agents from anti-amyloid aggregating AuNPs. Initially, we discuss the current status of anti-amyloid inhibitors, the abilities of AuNPs to inhibit amyloid aggregation, and mechanistic aspects, and then describe plausible modifications that could aid the translation of AuNP-based therapeutics into neuromedicines. The review highlights some interesting characteristics that might effectively bridge the gap between laboratory and bedside treatments.

scholarly journals Novel Perspective on Alzheimer’s Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid β

Life ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 118
Author(s):  
Arian Kola ◽  
Aleksandra Hecel ◽  
Stefania Lamponi ◽  
Daniela Valensin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rosmarinic Acid ◽  
Amyloid Β ◽  
Spectroscopic Techniques ◽  
Disease Treatment ◽  
Biological Assays ◽  
The Moment

Alzheimer’s disease is a severe disorder that affects millions of people worldwide. It is a very debilitating disease with no cure at the moment. The necessity of finding an effective treatment is very demanding, and the entire scientific community is putting in a lot of effort to address this issue. The major hallmark of Alzheimer’s disease is the presence of toxic aggregated species in the brain, impaired metal homeostasis, and high levels of oxidative stress. Rosmarinic acid is a well-known potent antioxidant molecule, the efficacy of which has been proved both in vitro and in vivo. In this study, we investigated the possible role played by rosmarinic acid as a mediator of the copper(II)-induced neurotoxicity. Several spectroscopic techniques and biological assays were applied to characterize the metal complexes and to evaluate the cytotoxicity and the mutagenicity of rosmarinic acid and its Cu(II) complex. Our data indicate that rosmarinic acid is able to interfere with the interaction between amyloid β and Cu(II) by forming an original ternary association.

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