Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery.
Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery.
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DOI：
10.3389/fendo.2022.892758
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
内源性大麻素信号传导系统是一种复杂的脂质信号传导途径，调节脊椎动物和无脊椎动物系统的多种生理过程。在线虫中，内源性大麻素（EC）生物学的知识主要来自自由生活的模式物种秀丽隐杆线虫，其中ECS与线虫生物学的关键方面有关。C.以外线虫ECS的保守性和复杂性。线虫的ECS生物学在很大程度上是未表征的，破坏了对线虫的ECS生物学的理解，包括对人类，兽医和植物健康至关重要的物种。在这项研究中，我们利用公开的组学数据集，在计算机生物信息学和系统发育分析，以检查的存在，保护和生命阶段的表达谱的EC效应跨门线虫。我们的数据表明：（i）ECS在线虫门中广泛保守，包括在治疗和农业相关物种中;（ii）EC效应物似乎显示出进化枝和生活方式特异性的保守模式;（iii）丝虫物种具有减少的EC效应物补体;（iv）线虫和脊椎动物EC效应物之间存在关键差异;（V）生命阶段特异性、组织特异性和性别特异性EC效应物表达谱表明ECS在治疗相关寄生线虫中的作用。据我们所知，这项研究代表了线虫门ECS途径的最全面的表征，并告知我们对线虫ECS复杂性的理解。线虫ECS系统的基础知识将为关键线虫寄生虫的后续功能研究奠定基础，以支持新的药物靶点发现工作。
The endocannabinoid signalling (ECS) system is a complex lipid signalling pathway that modulates diverse physiological processes in both vertebrate and invertebrate systems. In nematodes, knowledge of endocannabinoid (EC) biology is derived primarily from the free-living model species Caenorhabditis elegans, where ECS has been linked to key aspects of nematode biology. The conservation and complexity of nematode ECS beyond C. elegans is largely uncharacterised, undermining the understanding of ECS biology in nematodes including species with key importance to human, veterinary and plant health. In this study we exploited publicly available omics datasets, in silico bioinformatics and phylogenetic analyses to examine the presence, conservation and life stage expression profiles of EC-effectors across phylum Nematoda. Our data demonstrate that: (i) ECS is broadly conserved across phylum Nematoda, including in therapeutically and agriculturally relevant species; (ii) EC-effectors appear to display clade and lifestyle-specific conservation patterns; (iii) filarial species possess a reduced EC-effector complement; (iv) there are key differences between nematode and vertebrate EC-effectors; (v) life stage-, tissue- and sex-specific EC-effector expression profiles suggest a role for ECS in therapeutically relevant parasitic nematodes. To our knowledge, this study represents the most comprehensive characterisation of ECS pathways in phylum Nematoda and inform our understanding of nematode ECS complexity. Fundamental knowledge of nematode ECS systems will seed follow-on functional studies in key nematode parasites to underpin novel drug target discovery efforts.
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影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
14.9
作者：
Dereeper A;Guignon V;Blanc G;Audic S;Buffet S;Chevenet F;Dufayard JF;Guindon S;Lefort V;Lescot M;Claverie JM;Gascuel O
通讯作者：
Gascuel O
影响因子：
6.7
作者：
Chicca, Andrea;Arena, Chiara;Manera, Clementina
通讯作者：
Manera, Clementina
影响因子：
1.9
作者：
Di Marzo, V;De Petrocellis, L;Melck, D
通讯作者：
Melck, D
影响因子：
--
作者：
Blankman, Jacqueline L.;Simon, Gabriel M.;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.