A perspective review on fatty acid amide hydrolase (FAAH) inhibitors as potential therapeutic agents

Tripathi, Rohit

doi:10.1016/j.ejmech.2019.111953

Cited by 76 publications

(66 citation statements)

References 171 publications

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“…Although CB1 and CB2 are the most extensively studied proteins of ECS, there are also important factors regarding other molecular targets. In the case of eCB degrading enzymes, MAGL and FAAH, it is important to distinguish between reversible and irreversible inhibition [66,67]. For MAGL, it was shown that its irreversible inhibitors, through prolonged inactivation of this enzyme, may cause physical dependence, CB1 desensitization, and impaired eCB-dependent synaptic plasticity [68].…”

Section: Molecular Mechanisms Of the Main Proteins Of Ecs-implicationmentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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Section: Molecular Mechanisms Of the Main Proteins Of Ecs-implicationmentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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“…Epidemiological studies and clinical trials showed that fatty acids are associated with cardiovascular diseases [ 1 , 2 , 3 , 4 , 5 ], neurological diseases [ 6 , 7 , 8 , 9 ], non-alcoholic fatty liver disease [ 10 , 11 , 12 , 13 ], allergic diseases [ 14 , 15 , 16 ], and so on. Evidence from metabolomics experiments indicates that they participate in the metabolic pathways of related diseases [ 8 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. For example, the free FA profile was found to be altered in both leukemia and pre-leukemic diseases, particularly C14:0, C16:0, and C18:0 [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Nutritional Indices for Assessing Fatty Acids: A Mini-Review

Chen

Liu

2020

IJMS

583

439

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Dietary fats are generally fatty acids that may play positive or negative roles in the prevention and treatment of diseases. In nature, fatty acids occur in the form of mixtures of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA), so their nutritional and/or medicinal values must be determined. Herein, we do not consider the classic indices, such as ∑SFA, ∑MUFA, ∑PUFA, ∑n-6 PUFA, ∑n-3 PUFA, and n-6 PUFA/n-3 PUFA; instead, we summarize and review the definitions, implications, and applications of indices used in recent years, including the PUFA/SFA, index of atherogenicity (IA), the index of thrombogenicity (IT), the hypocholesterolemic/hypercholesterolemic ratio (HH), the health-promoting index (HPI), the unsaturation index (UI), the sum of eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA), fish lipid quality/flesh lipid quality (FLQ), the linoleic acid/α-linolenic acid (LA/ALA) ratio, and trans fatty acid (TFA). Of these nutritional indices, IA and IT are the most commonly used to assess the composition of fatty acids as they outline significant implications and provide clear evidence. EPA + DHA is commonly used to assess the nutritional quality of marine animal products. All indices have their advantages and disadvantages; hence, a rational choice of which to use is critical.

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“…Recently, novel results have indicated proteins that serve important roles during the process of cancer development. FAAH is a membrane-bound protein belonging to serine hydrolase family of enzymes that plays a signi cant role in the termination of signalling of fatty acid amides (FAAs), a class of bioactive lipids, both in the central nervous system and in some cancer tissues [54]. Hypoxia-inducible factors play an important role in the development of tumors, therefore the study functions of Hypoxia-inducible factors are also indispensable about cancer samples (HIF1A) [40,55].…”

Section: Discussionmentioning

confidence: 99%

Selecting optimal reference genes for breast cancer research

Song¹,

Huang²,

Wu³

et al. 2020

Preprint

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Background Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is the most sensitive technique for evaluating gene expression levels. Choosing appropriate reference genes (RGs) is critical for normalizing and evaluating changes in the expression of target genes. However, uniform and reliable RGs for breast cancer research have not been identified, limiting the value of target gene expression studies. Here, we provide a novel approach for mining RGs by using the RNA-seq dataset to identify reliable and accurate RGs that can be applied to different types of breast cancer tissues and cell lines. Methods First, we compiled the transcriptome profiling data from the TCGA database involving 1217 samples to identify novel RGs and then ten genes (SF1, TARDBP, THRAP3, QRICH1, TRA2B, SRSF3, YY1, DNAJC8, RNF10, and RHOA) with relatively stable expression levels were chosen as novel candidate RGs. Additionally, six conventional RGs (ACTB, TUBA1A, RPL13A, B2M, GAPDH, and GUSB) were also selected. To determine and validate the optimal RGs we performed qRT-PCR experiments on 87 samples from 5 types of surgically excised breast tumor specimens including HR+HER2-, HR+HER2+, HR-HER2-, HR-HER2+, breast cancer after neoadjuvant chemotherapy (NAC) and their matched para-carcinoma tissues, furthermore, we also included a benign breast tumor sample. Six biological replicates were included for each tissue. Moreover, we assessed 7 breast cancer cell lines (MCF-10A, MCF-7, T-47D, MDA-MB-231, MDA-MB-468, as well as MDA-MB-231 with either CNR2 knockdown or overexpression; 3 biological replicates for each line). Five statistical algorithms (geNorm, NormFinder, ΔCt method, BestKeeper, and ComprFinder) were used to assess the stability of expression of each RG across all breast cancer tissues and cell lines. Results Our results show that RG combinations SF1+TRA2B+THRAP3 and THRAP3+RHOA+QRICH1 showed stable expression in breast cancer tissues and cell lines, respectively, and that these two combinations displayed good interchangeability. Therefore, we propose that the above two combinations are optimal triplet RGs for breast cancer research. Conclusions In summary, we identified novel and reliable RG combinations for breast cancer research based on a public RNA-seq dataset which lays a solid foundation for accurate normalization of qRT-PCR results across different breast cancer tissues and cells.

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A perspective review on fatty acid amide hydrolase (FAAH) inhibitors as potential therapeutic agents

Cited by 76 publications

References 171 publications

A Guide to Targeting the Endocannabinoid System in Drug Design

A Guide to Targeting the Endocannabinoid System in Drug Design

Nutritional Indices for Assessing Fatty Acids: A Mini-Review

Selecting optimal reference genes for breast cancer research

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