Mefenamic Acid Shows Neuroprotective Effects and Improves Cognitive Impairment in in Vitro and in Vivo Alzheimer's Disease Models

2005 ◽  
Vol 69 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Yuyoung Joo ◽  
Hye-Sun Kim ◽  
Ran-Sook Woo ◽  
Cheol Hyoung Park ◽  
Ki-Young Shin ◽  
...  
2019 ◽  
Vol 356 ◽  
pp. 18-40 ◽  
Author(s):  
Priyal Barai ◽  
Nisith Raval ◽  
Sanjeev Acharya ◽  
Ankit Borisa ◽  
Hardik Bhatt ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-27 ◽  
Author(s):  
Samuele Maramai ◽  
Mohamed Benchekroun ◽  
Moustafa T. Gabr ◽  
Samir Yahiaoui

Neurodegenerative diseases represent nowadays one of the major health problems. Despite the efforts made to unveil the mechanism leading to neurodegeneration, it is still not entirely clear what triggers this phenomenon and what allows its progression. Nevertheless, it is accepted that neurodegeneration is a consequence of several detrimental processes, such as protein aggregation, oxidative stress, and neuroinflammation, finally resulting in the loss of neuronal functions. Starting from these evidences, there has been a wide search for novel agents able to address more than a single event at the same time, the so-called multitarget-directed ligands (MTDLs). These compounds originated from the combination of different pharmacophoric elements which endowed them with the ability to interfere with different enzymatic and/or receptor systems, or to exert neuroprotective effects by modulating proteins and metal homeostasis. MTDLs have been the focus of the latest strategies to discover a new treatment for Alzheimer’s disease (AD), which is considered the most common form of dementia characterized by neurodegeneration and cognitive dysfunctions. This review is aimed at collecting the latest and most interesting target combinations for the treatment of AD, with a detailed discussion on new agents with favorable in vitro properties and on optimized structures that have already been assessed in vivo in animal models of dementia.


Neuroscience ◽  
2018 ◽  
Vol 394 ◽  
pp. 72-82 ◽  
Author(s):  
Jing-Yi Liu ◽  
Xiao-Xin Chen ◽  
Hai-Yong Chen ◽  
Jun Shi ◽  
George Pak-Heng Leung ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Teng Ma ◽  
Meng-Shan Tan ◽  
Jin-Tai Yu ◽  
Lan Tan

Alzheimer’s disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβaccumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.


2020 ◽  
Vol 21 (22) ◽  
pp. 8672
Author(s):  
Federica Saponaro ◽  
Jin Hae Kim ◽  
Grazia Chiellini

Transthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in β-chains in a globular tetrameric protein, accounts for the predisposition of the protein to aggregate in fibrils, leading to a rare and severe disease, namely transthyretin amyloidosis (ATTR). Much effort has been made and still is required to find new therapeutic compounds that can stabilize TTR (“kinetic stabilization”) and prevent the amyloid genetic process. Moreover, TTR is an interesting therapeutic target for neurodegenerative diseases due to its recognized neuroprotective properties in the cognitive impairment context and interestingly in Alzheimer’s disease (AD). Much evidence has been collected regarding the neuroprotective effects in AD, including through in vitro and in vivo studies as well as a wide range of clinical series. Despite this supported hypothesis of neuroprotection for TTR, the mechanisms are still not completely clear. The aim of this review is to highlight the most relevant findings on the neuroprotective role of TTR, and to summarize the recent progress on the development of TTR tetramer stabilizers.


Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1952 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Kim ◽  
Eunjin Sohn ◽  
Jiyeon Yoon ◽  
Bu-Yeo Kim ◽  
...  

Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- β (Aβ) aggregation, β-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aβ-injected, Aβ-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aβ-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aβ aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H2O2)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aβ-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aβ aggregation and expression, as well as expression of Aβ, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aβ-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer’s disease.


2021 ◽  
Vol 19 ◽  
Author(s):  
Grazia D’Onofrio ◽  
Seyed Mohammad Nabavi ◽  
Daniele Sancarlo ◽  
Antonio Greco ◽  
Stefano Pieretti

: Crocus sativus L. (saffron) appears to own neuroprotective effects on cognitive impairment in patients with Alzheimer’s disease (AD). The purpose of this work is to review the evidence and mechanisms of saffron-induced therapeutic outcomes and measureable cognitive benefits in AD. The literature was reviewed, and preclinical and clinical studies were identified. In vitro and in vivo preclinical studies were selected according to these criteria: 1) development of saffron pharmacological profile on biological or biophysical endpoints; 2) evaluation of saffron efficacy using animal screens as an AD model, and 3) duration of the studies of at least 3 months. As for the clinical studies, the selection criteria included: 1) patients aged ≥ 60, 2) AD diagnosis according to National Institute on Aging-Alzheimer's Association (NIAAA) criteria, and 3) appropriate procedures to assess cognitive, functional, and clinical status. A total of 1477 studies published until November 2020 were identified during an initial phase, of which 24 met the inclusion criteria and were selected for this review. Seventeen in vitro and in vivo preclinical studies have described the efficacy of saffron on cognitive impairment in animal models of AD, highlighting that crocin appears to be able to regulate glutamate levels, reduce oxidative stress, and modulate Aβ and tau protein aggregation. Only four clinical studies have indicated that the effects of saffron on cognitive impairment were not different from those produced by donepezil and memantine and that it had a better safety profile. Saffron and its compounds should be further investigated in order to consider them a safer alternative in AD treatment.


2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.


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