A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease

Pathak, Chandni; Kabra, Uma D.

doi:10.1016/j.bioorg.2024.107152

Cited by 19 publications

(4 citation statements)

References 105 publications

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“…Also, stilbenes were again strongly correlated with our in vitro findings, recording a significant correlation coefficient (0.767; p < 0.01). Consistently, several researchers have found stilbenes to be significant inhibitors [ 48 , 49 ] of intestinal enzymes, with some dimeric stilbenoids (such as viniferin isomers) described to be better than the reference drug acarbose in inhibiting the pancreatic α-amylase [ 50 ]. Coherently, our findings revealed a great abundance of stilbenoids at the intestinal level, such as e-viniferin and resveratrol derivatives, likely explaining the results obtained.…”

Section: Resultsmentioning

confidence: 91%

Impact of In Vitro Gastrointestinal Digestion on the Phenolic Bioaccessibility and Bioactive Properties of Insect-Containing Beef Burgers

Rocchetti,

Zengin,

Giuberti

et al. 2024

Antioxidants

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Mealworm, migratory locust, and house cricket have recently been recognized by the European Commission as novel foods, thus being suitable in different food applications. In this work, we tested their powders as meat extenders at 5% (w/w) inclusion in beef burgers, considering their ability to vehicle phenolic compounds during simulated in vitro static gastrointestinal digestion (INFOGEST). Insect powders were abundant in different phenolic classes, recording the highest values in locust (LP; 314.69 mg/kg), followed by cricket (CP; 113.3 mg/kg) and mealworm (MWP; 51.9 mg/kg). Following a pan-cooking process, LP burgers were confirmed as the best source of phenolics, with a marked abundance of flavonoids and phenolic acids. Interestingly, the insect powders were found to affect the in vitro gastrointestinal bioaccessibility of phenolic compounds when compared with the CTR burger, likely promoted by the interactions between the phenolic compounds and proteins characterizing the tested insect powders. Among the most discriminant phenolic metabolites at the gastrointestinal level, we found several phenolic acids (mainly hydroxycinnamics), recording the highest content for the digested CP-containing burgers. Finally, stilbenes showed significant correlation values at the intestinal level with both antioxidant and enzymatic activities, while total flavonoids were the most correlated with the inhibition of acetylcholinesterase. Taken together, our preliminary findings demonstrated that insect powders added to beef burgers can promote the bioaccessibility and potential bioavailability of phenolics in the distal tracts of the intestine.

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Section: Resultsmentioning

confidence: 91%

Impact of In Vitro Gastrointestinal Digestion on the Phenolic Bioaccessibility and Bioactive Properties of Insect-Containing Beef Burgers

Rocchetti,

Zengin,

Giuberti

et al. 2024

Antioxidants

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show abstract

“…The field of the multitarget approach may thus provide innovative therapeutic solutions to feed the pipeline of disease-modifying drugs for AD and PD. The potential of the multitarget approach in discovering new drug candidates for multifactorial diseases such as AD and PD was extensively reviewed in [ 294 , 297 , 298 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Sequeira,

Benfeito,

Fernandes

et al. 2024

Pharmaceutics

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Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

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“…As opposed to AChE, the exact biological role of BChE is not well-known. It is reported that BChE participates in various human diseases, such as cardiovascular disease ( Goliasch et al, 2012 ), diabetes ( Sridhar et al, 2010 ), hypercholesterolemia ( Wang et al, 2022 ) and neurodegenerative disorders ( Jasiecki et al, 2021 ; Pathak and Kabra, 2024 ). Studies have shown that the therapeutic strategy of inhibiting BChE activity can effectively improve cognitive function in patients with Alzheimer’s disease (AD) ( Macdonald et al, 2017 ; De Candia et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors

Li,

Yan

et al. 2024

Front. Bioeng. Biotechnol.

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Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer’s disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%–104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.

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A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease

Cited by 19 publications

References 105 publications

Impact of In Vitro Gastrointestinal Digestion on the Phenolic Bioaccessibility and Bioactive Properties of Insect-Containing Beef Burgers

Impact of In Vitro Gastrointestinal Digestion on the Phenolic Bioaccessibility and Bioactive Properties of Insect-Containing Beef Burgers

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors

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