Antioxidant as Talented Drug Applicants for the Treatment of Alzheimer’s Disease and their Molecular Mechanism Insights

2020 ◽  
Vol 26 ◽  
Author(s):  
Rokeya Akter ◽  
Md. Arifur Rahman Chowdhury ◽  
Md. Habib ur Rahman

: Alzheimer's disease (AD), with no preventive or curative therapy, is the most prevalent neurodegenerative condition to date. Histopathological features of AD include β-amyloid plate deposition and neurofibrillary tangles development. Extensive pathology studies have provided significant results concerning disease processes and therapeutic objectives. Some cellular changes, including oxidative stress, Ca2 + homeostasis, flame retardation, metabolic disorders, and protein accumulation, that lead to programmed cell death. AD is a cause of cellular changes. Despite extensive study, only five licensed medicines for AD management are available. Alternative therapies must also be considered. Over the last years, it has gained interest through the use of natural ingredients and culinary herbs. Many natural substances have been extensively researched with neuroprotective effects. Some of these compound products have amazing antioxidant properties and are primarily used by free radical species. Others enhance cell survival and cognition by influencing amyloidogenesis and programmed cell death. Further research on these natural products and their modes of action, along with the application of new drug design and methods of delivery; allow us to add conventional medicine. In this report, many natural antioxidant products with possible neuroprotective characteristics against Aβ were discussed in their mechanism of action.

2006 ◽  
Vol 14 (7S_Part_20) ◽  
pp. P1083-P1083
Author(s):  
Daniela Lecca ◽  
Miaad Bader ◽  
David Tweedie ◽  
Debomoy K. Lahiri ◽  
Robert E. Becker ◽  
...  

Author(s):  
Yulian Zou ◽  
Chen-Ling Gan ◽  
Zhiming Xin ◽  
Hai-Tao Zhang ◽  
Qi Zhang ◽  
...  

Alzheimer’s disease (AD) is a central nervous system degenerative disease, with no effective treatment to date. Administration of immune checkpoint inhibitors significantly reduces neuronal damage and tau hyperphosphorylation in AD, but the specific mechanism is unclear. Here, we found that programmed cell death-receptor 1 (PD1) and its ligand PDL1 were induced by an intracerebroventricular injection of amyloid-β; they were significantly upregulated in the brains of APP/PS1, 5×FAD mice and in SH-SY5Y-APP cell line compared with control. The PD1 and PDL1 levels positively correlated with the glycogen synthase kinase 3 beta (GSK3β) activity in various AD mouse models, and the PDL1-GSK3β immune complex was found in the brain. The application of PD1-blocking antibody reduced tau hyperphosphorylation and GSK3β activity and prevented memory impairments. Mechanistically, we identified PD1 as a critical regulator of GSK3β activity. These results suggest that the immune regulation of the PD1/PDL1 axis is closely involved in AD.


2010 ◽  
Vol 7 (1-3) ◽  
pp. 60-63 ◽  
Author(s):  
David S. Greenberg ◽  
Debra Toiber ◽  
Amit Berson ◽  
Hermona Soreq

2018 ◽  
Vol 15 (9) ◽  
pp. 883-891 ◽  
Author(s):  
Robert E. Becker ◽  
Nigel H. Greig ◽  
Debomoy K. Lahiri ◽  
Joseph Bledsoe ◽  
Sarah Majercik ◽  
...  

Background: Concussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities. Multiple clinical trials targeting mechanisms based on the Amyloid Hypothesis of AD have so far failed, indicating that it is prudent for new drug developments to also pursue mechanisms independent of the Amyloid Hypothesis. To address these issues, we have proposed the use of an animal model of concussion/TBI as a supplement to AD transgenic mice to provide an indication of an AD drug candidate’s potential for preventing PPCD and resulting progression towards dementia in AD. Methods: We searched PubMed/Medline and the references of identified articles for background on the neuropathological progression of AD and its implications for drug target identification, for AD clinical trial criteria used to assess disease modification outcomes, for plasma biomarkers associated with AD and concussion/TBI, neuropathologies and especially PPCD, and for methodological critiques of AD and other neuropsychiatric clinical trial methods. Results: We identified and address seven issues and highlight the Thal-Sano AD ‘Time to Onset of Impairment' Design for possible applications in our clinical trials. Diverse and significant pathological cascades and indications of self-induced neuronal PPCD were found in concussion/TBI, anoxia, and AD animal models. To address the dearth of peripheral markers of AD and concussion/TBI brain pathologies and PPCD we evaluated Extracellular Vesicles (EVs) enriched for neuronal origin, including exosomes. In our concussion/TBI, anoxia and AD animal models we found evidence consistent with the presence of time-dependent PPCD and (-)-phenserine suppression of neuronal self-induced PPCD. We hence developed an extended controlled release formulation of (-)-phenserine to provide individualized dosing and stable therapeutic brain concentrations, to pharmacologically interrogate PPCD as a drug development target. To address the identified problems potentially putting any clinical trial at risk of failure, we developed exploratory AD and concussion/TBI clinical trial designs. Conclusions: Our findings inform the biomarker indication of progression of pathological targets in neurodegenerations and propose a novel approach to these conditions through neuronal protection against self-induced PPCD.


2014 ◽  
Vol 50 (2) ◽  
pp. 463-472 ◽  
Author(s):  
Beatrice Macchi ◽  
Francesca Marino-Merlo ◽  
Caterina Frezza ◽  
Salvatore Cuzzocrea ◽  
Antonio Mastino

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 59 ◽  
Author(s):  
Haroon Khan ◽  
Hammad Ullah ◽  
Michael Aschner ◽  
Wai San Cheang ◽  
Esra Küpeli Akkol

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer’s disease and its potential as a lead compound in clinical applications.


2021 ◽  
Vol 28 ◽  
Author(s):  
Arian Kola ◽  
Dorota Dudek ◽  
Daniela Valensin

: Polyphenols are a class of compounds produced by plants, which share the ability to act as potent antioxidants. First investigations on polyphenols’ antioxidant activity are dated almost twenty years ago when their relationship and implication with the prevention and treatment of cancer was proposed for the first time. Later, in the early 2000s, the neuroprotective effects of several polyphenols were demonstrated. Nowadays, the benefits of a plethora of polyphenols have been studied, and their ameliorating effects in several disease conditions, like cancer, cardiac and neuronal diseases, are widely recognized. More than 1000 papers dealing with polyphenols and Alzheimer’s disease have been published so far, describing the antioxidant properties, the chelating metal features, and the anti-aggregating behavior of these compounds. This review aims to rationalize, from a chemical point of view, the metal complexation mechanisms of polyphenols related to two significant events of Alzheimer’s disease: oxidative stress and metal ion dyshomeostasis. To address this issue, we have herein discussed several aspects implicated in Alzheimer’s disease and polyphenols involved in treating the disease.


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