从[来源]获得的神经活性毒液化合物作为神经退行性疾病的潜在先导物：对其乙酰胆碱酯酶和β-分泌酶抑制活性的见解 。 （注：原文中“from as potential leads for neurodegenerative diseases”里“from”后缺少具体来源信息，这里按字面翻译为“从[来源]” ）
Neuroactive venom compounds obtained from as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities .
作者信息
Lopez Simon Miguel M, Aguilar Jeremey S, Fernandez Jerene Bashia B, Lao Angelic Gayle J, Estrella Mitzi Rain R, Devanadera Mark Kevin P, Ramones Cydee Marie V, Villaraza Aaron Joseph L, Guevarra Leonardo A, Santiago-Bautista Myla R, Santiago Librado A
机构信息
Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.
Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Philippines, 1101.
出版信息
J Venom Anim Toxins Incl Trop Dis. 2021 Jun 28;27:e20210009. doi: 10.1590/1678-9199-JVATITD-2021-0009. eCollection 2021.
BACKGROUND
Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of venom against neurodegenerative diseases.
METHODS
Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from larvae and fractions were screened for their inhibitory activities against AChE and BACE .
RESULTS
The whole venom from demonstrated neuroactivity by inducing excitatory movements from for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control.
CONCLUSION
The venom of contains compounds that demonstrate neuroactivity and anti-AChE activities , which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.
背景
蜘蛛毒液是一种富含神经活性化合物的混合物，旨在捕食猎物并抵御捕食者，这些化合物作用于神经元膜蛋白，特别是乙酰胆碱酯酶（AChE），它通过水解乙酰胆碱（ACh，一种兴奋性神经递质）来调节突触传递，以及β-分泌酶（BACE），其主要切割淀粉样前体蛋白（APP），而APP又与神经元的结构完整性相关。本研究提供了蜘蛛毒液对神经退行性疾病治疗潜力的初步证据。
方法
通过电刺激提取蜘蛛毒液，并用反相高效液相色谱（RP-HPLC）进行分离，通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）进行表征。通过观察幼虫的神经行为反应来检测全毒液的神经活性，并筛选各组分对AChE和BACE的抑制活性。
结果
来自[蜘蛛名称未给出]的全毒液通过诱导[幼虫名称未给出]产生兴奋运动达15分钟，从而表现出神经活性。收集的16个组分通过MALDI-TOF-MS产生了900 - 4500 Da范围内的不同质量片段。16个组分中有11个表现出AChE抑制活性，与多奈哌齐（抑制率为86.34%（± 3.90e-5））相比，抑制率为14.34%（± 2.60e-4）至62.05%（± 6.40e-5）（p > 0.05），而未观察到任何组分表现出BACE抑制活性。此外，与作为阳性对照的多奈哌齐相比，针对AChE的三个有效组分F1、F3和F16表现出竞争性和非竞争性抑制作用。
结论
[蜘蛛名称未给出]的毒液含有具有神经活性和抗AChE活性的化合物，这可能为开发针对神经疾病的胆碱能化合物提供潜在的治疗线索。
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