Neurotoxin

神经毒素
  • 文章类型: Journal Article
    帕金森病是一种以进行性运动障碍为特征的复杂神经退行性疾病。主要症状包括静息性震颤,运动迟缓,肢体僵硬,和姿势不稳定。此外,它还包括一系列非运动症状,如睡眠障碍,失足,胃肠功能障碍,自主神经功能障碍和认知障碍。病理上,该疾病表现为多巴胺能神经元丢失和路易体的存在。目前,帕金森病的临床治疗没有取得重大突破。探索治疗方式需要建立科学合理的动物模型。近年来,研究人员专注于复制人类帕金森病的症状,主要通过药物和转基因方法建立各种实验动物模型,以模拟相关病理并确定更有效的治疗方法。这篇综述研究了传统的神经毒素和转基因动物模型以及α-突触核蛋白预形成的原纤维模型,非人灵长类动物模型和非哺乳动物物种模型。此外,它引入了新兴的模型,包括基于光遗传学的模型,诱导多能干细胞,和基因编辑,旨在为该领域的研究人员利用实验动物模型和临床研究提供参考。
    Parkinson\'s disease is a complex neurodegenerative disease characterized by progressive movement impairments. Predominant symptoms encompass resting tremor, bradykinesia, limb rigidity, and postural instability. In addition, it also includes a series of non-motor symptoms such as sleep disorders, hyposmia, gastrointestinal dysfunction, autonomic dysfunction and cognitive impairment. Pathologically, the disease manifests through dopaminergic neuronal loss and the presence of Lewy bodies. At present, no significant breakthrough has been achieved in clinical Parkinson\'s disease treatment. Exploring treatment modalities necessitate the establishment of scientifically sound animal models. In recent years, researchers have focused on replicating the symptoms of human Parkinson\'s disease, resulting in the establishment of various experimental animal models primarily through drugs and transgenic methods to mimic relevant pathologies and identify more effective treatments. This review examines traditional neurotoxin and transgenic animal models as well as α-synuclein pre-formed fibrils models, non-human primate models and non-mammalian specie models. Additionally, it introduces emerging models, including models based on optogenetics, induced pluripotent stem cells, and gene editing, aiming to provide a reference for the utilization of experimental animal models and clinical research for researchers in this field.
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  • 文章类型: Journal Article
    铝(Al)被认为是神经毒素。研究证实Al诱导的神经毒性可能与tau蛋白过度磷酸化有关。磷酸化tau通过泛素-蛋白酶体途径(UPP)降解,其中Hsc70相互作用蛋白(CHIP)的羧基末端起着重要作用。然而,CHIP是否在调节Al诱导的tau过度磷酸化中起作用尚待确定。本研究旨在探讨CHIP在AlCl3诱导的N2a细胞tau过度磷酸化中的分子机制。将小鼠神经母细胞瘤细胞(N2a)暴露于不同浓度的AlCl3(0、0.5、1和2mM),并用CHIP/CHIPshRNA/CHIP(ΔU-box)/CHIP(ΔTPR)质粒转染处理。通过CCK-8试剂盒测定细胞活力。蛋白质印迹法检测蛋白质表达。通过阶乘设计ANOVA分析了CHIP和AlCl3暴露在蛋白质上的相互作用。结果表明Al可引起tau蛋白过度磷酸化,主要影响N2a细胞中tau的pThr231、pSer262和pSer396位点。UPP参与Al诱导的N2a细胞中tau过度磷酸化的降解,其中芯片可能是主要的监管目标。CHIP的U-box和TPR结构域都是必不可少的,并且在调节N2a细胞中AlCl3诱导的tau过度磷酸化中起重要作用。
    Aluminum (Al) is recognized as a neurotoxin. Studies have confirmed that the neurotoxicity induced by Al may be related to tau hyperphosphorylation. Phosphorylated tau is degraded through the ubiquitin-proteasome pathway (UPP), in which the carboxyl terminus of Hsc70-interacting protein (CHIP) plays an important role. However, whether the CHIP plays a role in regulating tau hyperphosphorylation induced by Al is yet to be determined. The purpose of this study was to explore the molecular mechanism of the CHIP in tau hyperphosphorylation induced by AlCl3 in N2a cells. Mouse neuroblastoma cells (N2a) were exposed to different concentrations of AlCl3 (0, 0.5, 1, and 2 mM) and treated with CHIP/CHIP shRNA/CHIP (ΔU-box)/CHIP (ΔTPR) plasmid transfection. The cell viability was determined by the CCK-8 kit. Protein expression was detected by Western blot. The interaction between CHIP and AlCl3 exposure on the proteins was analyzed by factorial design ANOVA. The results showed that Al can cause tau hyperphosphorylation, mainly affecting the pThr231, pSer262, and pSer396 sites of tau in N2a cells. UPP is involved in the degradation of tau hyperphosphorylation induced by Al in N2a cells, of which CHIP may be the main regulatory target. Both the U-box and TPR domains of CHIP are indispensable and play an important role in the regulation of tau hyperphosphorylation induced by AlCl3 in N2a cells.
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  • 文章类型: Journal Article
    免疫疗法是一种有前途的癌症治疗方法。其中,针对PD-1/PD-L1的免疫检查点抑制剂越来越多地用于某些癌症.然而,随着这些药物的广泛使用,免疫相关不良事件(irAE)的报告也在增加.神经不良事件(nAE)是影响外周和中枢神经系统的irAE之一。它们的特点是发病率低,很难诊断,和危及生命的风险,对患者的预后有显著影响。基于生物标志物的早期诊断和后续治疗策略值得关注。综合管理irAE对于优化患者的生活质量和长期结局非常重要。在这次审查中,我们总结了机制,常见症状,早期生物标志物,治疗,以及NAE未来的研究方向,以提供针对PD-1/PD-L1的免疫检查点抑制剂相关nAE的全面概述。
    Immunotherapy is a promising method for cancer treatment. Among them, immune checkpoint inhibitors targeting PD-1/PD-L1 are increasingly used for certain cancers. However, with the widespread use of such drugs, reports of immune-related adverse events (irAEs) are also increasing. Neurological adverse events (nAEs) are one of the irAEs that affect the peripheral and central nervous systems. They are characterized by low incidence, hard to diagnose, and life-threatening risks, which have a significant impact on the prognosis of patients. Biomarker-based early diagnosis and subsequent treatment strategies are worthy of attention, and comprehensive management of irAEs is important for optimizing patients\' quality of life and long-term outcomes. In this review, we summarized the mechanisms, common symptoms, early biomarkers, treatments, and future research directions of nAEs, in order to provide a comprehensive overview of immune checkpoint inhibitor-related nAEs targeting PD-1/PD-L1.
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  • 文章类型: Journal Article
    角膜轨迹(LC)位于脑干中,并向关键的大脑结构提供去甲肾上腺素,包括前脑和海马体.LC影响特定行为,如焦虑,恐惧,和动机,以及影响大脑功能的生理现象,包括睡眠,血流调节,和毛细管通透性。然而,LC功能障碍的短期和长期后果尚不清楚.LC是首先在患有神经退行性疾病如帕金森病和阿尔茨海默病的患者中受到影响的大脑结构之一。提示LC功能障碍可能在疾病的发展和进展中起重要作用。改变或破坏LC功能的动物模型对于进一步了解正常大脑中的LC功能至关重要。LC功能障碍的后果,及其在疾病发展中的作用。为此,需要明确表征的LC功能障碍动物模型。这里,我们建立了用于LC消融的选择性神经毒素N-(2-氯乙基)-N-乙基-溴-苄胺(DSP-4)的最佳剂量。使用组织学和体视学,我们比较了LC消融(LCA)小鼠和对照组的LC体积和神经元数量,以评估不同DSP-4注射次数的LC消融的疗效.所有LCA组显示LC细胞计数和LC体积的一致降低。然后,我们使用明暗箱测试来表征LCA小鼠的行为,巴恩斯迷宫测试,和非侵入性睡眠觉醒监测。行为上,LCA小鼠与对照小鼠略有不同,与已知的LC功能和预测一致的对照相比,LCA小鼠通常更好奇和更少焦虑。我们注意到一个有趣的对比,即对照小鼠具有不同的LC大小和神经元计数,但行为一致,而LCA小鼠(如预期)具有一致的LC大小,但行为不稳定。我们的研究提供了LC消融模型的全面表征,巩固其作为研究LC功能障碍的有效模型系统。
    The Locus Coeruleus (LC) is in the brainstem and supplies key brain structures with noradrenaline, including the forebrain and hippocampus. The LC impacts specific behaviors such as anxiety, fear, and motivation, as well as physiological phenomena that impact brain functions in general, including sleep, blood flow regulation, and capillary permeability. Nevertheless, the short- and long-term consequences of LC dysfunction remain unclear. The LC is among the brain structures first affected in patients suffering from neurodegenerative diseases such as Parkinson\'s disease and Alzheimer\'s Disease, hinting that LC dysfunction may play a central role in disease development and progression. Animal models with modified or disrupted LC function are essential to further our understanding of LC function in the normal brain, the consequences of LC dysfunction, and its putative roles in disease development. For this, well-characterized animal models of LC dysfunction are needed. Here, we establish the optimal dose of selective neurotoxin N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP-4) for LC ablation. Using histology and stereology, we compare LC volume and neuron number in LC ablated (LCA) mice and controls to assess the efficacy of LC ablation with different numbers of DSP-4 injections. All LCA groups show a consistent decrease in LC cell count and LC volume. We then proceed to characterize the behavior of LCA mice using a light-dark box test, Barnes maze test, and non-invasive sleep-wakefulness monitoring. Behaviorally, LCA mice differ subtly from control mice, with LCA mice generally being more curious and less anxious compared to controls consistent with known LC function and projections. We note an interesting contrast in that control mice have varying LC size and neuron count but consistent behavior whereas LCA mice (as expected) have consistently sized LC but erratic behavior. Our study provides a thorough characterization of an LC ablation model, firmly consolidating it as a valid model system for the study of LC dysfunction.
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  • 文章类型: Journal Article
    神经毒素是一类对神经组织具有显著损伤作用的蛋白质。神经毒素分为突触前神经毒素和突触后神经毒素,神经毒素的准确鉴定在药物开发中起着关键作用。在这项研究中,对90种突触前神经毒素和165种突触后神经毒素进行了分类。使用AutoProp特征提取方法提取突触前和突触后神经毒素序列的特征,并使用最大相关最大距离(MRMD)程序进行特征选择,最后,仅保留2个特征,达到84.7%的分类准确率.此外,发现这两个保留的特征存在于突触前神经毒素的保守位点和基序中,并且可以代表突触前神经毒素的关键结构。该方法表明,使用一些关键特征对蛋白质进行分类可以有效地识别关键的蛋白质结构。
    Neurotoxins are a class of proteins that have a significant damaging effect on nerve tissue. Neurotoxins are classified into presynaptic neurotoxins and postsynaptic neurotoxins, and accurate identification of neurotoxins plays a key role in drug development. In this study, 90 presynaptic neurotoxins and 165 postsynaptic neurotoxins were classified. The features of the presynaptic and postsynaptic neurotoxin sequences were extracted using the AutoProp feature extraction method and feature selection was performed using the maximum relevance maximum distance (MRMD) program, Finally, only two features were retained to achieve 84.7% classification accuracy. Moreover, it was found that the two retained features were present in the conserved sites and motifs of presynaptic neurotoxins and could represent the critical structures of presynaptic neurotoxins. This method demonstrates that using a few key features to classify proteins can effectively identify critical protein structures.
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  • 文章类型: Journal Article
    马蹄蟹(HSC)是一组具有重要生态和生物医学意义的古老螯合物。食用亚洲HSC引起的食物中毒对公众健康和安全有重大影响。这项研究于2020年5月测量了北部湾北部不同生命阶段的两种HSC物种中的河豚毒素(TTX)浓度。它们在中国最重要的产卵和育苗栖息地。圆锥花和Tudentatus的平均TTX含量范围为6.2-8.0μg/kg和3.8-8.4μg/kg,分别。采样位置时,生长和蜕皮阶段对两种物种的TTX分布影响很小,血淋巴中检测到明显更高水平的TTX,但在早龄幼年三叉戟的合并组织中较低。这些结果提供了产卵季节HSC中TTX发生和分布的区域视图。这对于未来研究增强对HSC中TTX动力学和形成的理解至关重要。
    Horseshoe crabs (HSCs) are a group of ancient chelicerates with great ecological and biomedical importance. Food poisonings caused by the consumption of Asian HSCs have significant impacts on public health and safety. This study measured tetrodotoxin (TTX) concentrations in two HSC species across various life stages in May 2020 from the northern Beibu Gulf, their most important spawning and nursery habitats in China. The average TTX contents in both Carcinoscorpius rotundicauda and Tachypleus tridentatus ranged 6.2-8.0 μg/kg and 3.8-8.4 μg/kg, respectively. While sampling location, growth and molt stages have little influence on TTX distribution in both species, significantly higher levels of TTX were detected in hemolymph, but lower in pooled tissues of early-instar juvenile T. tridentatus. These results provide a regional view of TTX occurrence and distribution in HSCs during their spawning season, which are critical for future studies to enhance understanding of TTX dynamics and formation in HSCs.
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  • 文章类型: Journal Article
    抑郁症可能是非运动症状,一个风险因素,甚至是帕金森病(PD)的合并症。无论哪种情况,抑郁症严重影响PD患者的生活质量。不幸的是,目前,大量的临床和基础研究集中在PD的病理生理机制和运动症状的预防和治疗上。尽管人们越来越关注与PD相关的抑郁症,很难做到早期发现和早期干预,因为临床指南主要是指在运动障碍后或伴有运动障碍后出现的抑郁症。为什么会有这样的困境?这是因为没有合适的临床前动物模型来研究抑郁症与PD之间的关系,在PD临床前模型中评估抑郁行为也是一项非常具有挑战性的任务,因为它并非没有运动障碍的混杂因素。作为模拟PD症状的常用方法,神经毒素诱导的PD模型已被广泛使用。研究发现,神经毒素诱导的PD模型动物可以表现出抑郁样行为,有时比运动障碍更早表现出来。因此,已经尝试通过神经毒素诱导建立PD相关抑郁模型.然而,由于缺乏统一的协议,报告的结果多种多样.为了进一步促进动物模型的改进和优化以及PD相关抑郁症的研究,我们根据现有文献和我们自己的研究经验,回顾了目前PD相关抑郁动物模型的建立和评估策略,并讨论了可能的机制和干预措施,以期为今后这方面的研究提供参考。
    Depression can be a non-motor symptom, a risk factor, and even a co-morbidity of Parkinson\'s disease (PD). In either case, depression seriously affects the quality of life of PD patients. Unfortunately, at present, a large number of clinical and basic studies focused on the pathophysiological mechanism of PD and the prevention and treatment of motor symptoms. Although there has been increasing attention to PD-related depression, it is difficult to achieve early detection and early intervention, because the clinical guidelines mostly refer to depression developed after or accompanied by motor impairments. Why is there such a dilemma? This is because there has been no suitable preclinical animal model for studying the relationship between depression and PD, and the assessment of depressive behavior in PD preclinical models is as well a very challenging task since it is not free from the confounding from the motor impairment. As a common method to simulate PD symptoms, neurotoxin-induced PD models have been widely used. Studies have found that neurotoxin-induced PD model animals could exhibit depression-like behaviors, which sometimes manifested earlier than motor impairments. Therefore, there have been attempts to establish the PD-related depression model by neurotoxin induction. However, due to a lack of unified protocol, the reported results were diverse. For the purpose of further promoting the improvement and optimization of the animal models and the study of PD-related depression, we reviewed the establishment and evaluation strategies of the current animal models of PD-related depression based on both the existing literature and our own research experience, and discussed the possible mechanism and interventions, in order to provide a reference for future research in this area.
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  • 文章类型: Journal Article
    肉毒梭菌是肉毒杆菌中毒的致病病原体。肉毒杆菌的实验室检测对于肉毒杆菌中毒的临床治疗是必不可少的,尤其是婴儿肉毒中毒.肉毒神经毒素(BoNT)的极端毒性需要灵敏的检测方法。由于实时定量PCR(q-PCR)的检测限,一种更灵敏的检测方法,在肉毒杆菌主要血清型A和B中应用微滴数字PCR(ddPCR)。通过ddPCR评估以下性能标准:分析灵敏度;可重复性;和诊断特异性。BoNTA和B基因的检测限(LOD)为0.84和0.88拷贝/μl,分别,通过具有高特异性的ddPCR,通过q-PCR与5.04×102和6.91×102拷贝/μl进行比较。在加标粪便样品中,与q-PCR相比,它增加了10倍。这种灵敏度的提高在临床样品中尤其重要,因为与q-PCR相比,通过数字PCR检测到更多的阳性样品。同时,与q-PCR相比,ddPCR在A型和B型肉毒杆菌中的低细菌含量样品的富集时间缩短了4小时。这对实验室诊断和流行病学工作很重要。
    Clostridium botulinum is the causative pathogen of botulism. Laboratory detection of C. botulinum is essential for clinical therapy treatment of botulism due to the difficulty in diagnosis, especially in infant botulism. The extreme toxicity of botulinum neurotoxin (BoNT) requires a sensitive detection method. Due to the detection limit of real-time quantitative PCR (q-PCR), a more sensitive detection method, micro-drop digital PCR (ddPCR) was applied in C. botulinum main serotypes A and B. The following performance criteria were evaluated by ddPCR: analytical sensitivity; repeatability; and diagnostic specificity. The limit of detection (LOD) was 0.84 and 0.88 copies/μl for BoNT A and B genes, respectively, by ddPCR with high specificity, compared to 5.04×102 and 6.91×102 copies/μl by q-PCR. It was increased 10 times compared with q-PCR in spiked stool samples. This improvement in sensitivity was especially important in clinical samples as more positive samples were detected by digital PCR compared with q-PCR. Meanwhile, enrichment time for low bacteria content samples was shortened by four hours both in serotypes A and B C. botulinum by ddPCR compared with q-PCR, which are important for laboratory diagnosis and epidemiology work.
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  • 文章类型: Comparative Study
    帕金森病(PD)的动物模型对于了解PD的发病机制和筛选新的治疗方法非常有用。本研究比较了两种常用的神经毒素诱导的慢性PD小鼠模型,以指导模型选择,探索PD的发病机制和潜在机制,并开发有效的治疗方法。通过用鱼藤酮或1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)治疗6周建立慢性PD小鼠模型。通过评估神经行为来比较鱼藤酮和MPTP对小鼠的影响,通过使用极点的神经病理学和线粒体功能,旋转杆和开放式现场测试,酪氨酸羟化酶(TH)的免疫组织化学,胶质纤维酸性蛋白(GFAP),离子化钙结合接头分子1(Iba-1),神经元核抗原(NeuN)和(p)S129α-突触核蛋白,GFAP的免疫荧光,Iba‑1和NeuN,TH的西方印迹,耗氧量,复合物I酶活性。运动活动,与对照组相比,鱼藤酮和MPTP组的运动协调和探索行为均显着降低。然而,行为测试在两组间无显著差异.在MPTP组中,黑质(SN)中多巴胺能(DA)神经元的丢失,与鱼藤酮组相比,SN和纹状体中酪氨酸羟化酶含量的降低以及SN中星形胶质细胞的增殖和小胶质细胞的活化更为显着。值得注意的是,与MPTP组相比,鱼藤酮组的线粒体依赖性耗氧量和SN中的复合物I酶活性显着降低。此外,路易体仅存在于鱼藤酮组的SN神经元中。尽管在两种小鼠模型之间没有观察到神经行为的显着差异,MPTP模型在DA神经元丢失方面更精确地再现了PD的病理特征,多巴胺水平降低和SN中的神经炎症。另一方面,鱼藤酮模型更适合研究线粒体功能障碍(复合物I活性缺失)和路易体形成在SN中的作用,这是PD的特征性病理特征。结果表明,MPTP和鱼藤酮PD模型各有优缺点,因此,应根据研究目的选择一个或两个。
    Animal models for Parkinson\'s disease (PD) are very useful in understanding the pathogenesis of PD and screening for new therapeutic approaches. The present study compared two commonly used neurotoxin‑induced mouse models of chronic PD to guide model selection, explore the pathogenesis and mechanisms underlying PD and develop effective treatments. The chronic PD mouse models were established via treatment with rotenone or 1‑methyl‑4‑phenyl‑1,2,3,6-tetrahydropyridine (MPTP) for 6 weeks. The effects of rotenone and MPTP in the mice were compared by assessing neurobehavior, neuropathology and mitochondrial function through the use of the pole, rotarod and open field tests, immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), ionized calcium‑binding adapter molecule 1 (Iba‑1), neuronal nuclear antigen (NeuN) and (p)S129 α‑synuclein, immunofluorescence for GFAP, Iba‑1 and NeuN, western blotting for TH, oxygen consumption, complex I enzyme activity. The locomotor activity, motor coordination and exploratory behavior in both rotenone and MPTP groups were significantly lower compared with the control group. However, behavioral tests were no significant differences between the two groups. In the MPTP group, the loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta, the reduction of the tyrosine hydroxylase content in the SN and striatum and the astrocyte proliferation and microglial activation in the SN were more significant compared with the rotenone group. Notably, mitochondrial‑dependent oxygen consumption and complex I enzyme activity in the SN were significantly reduced in the rotenone group compared with the MPTP group. In addition, Lewy bodies were present only in SN neurons in the rotenone group. Although no significant differences in neurobehavior were observed between the two mouse models, the MPTP model reproduced the pathological features of PD more precisely in terms of the loss of DA neurons, decreased dopamine levels and neuroinflammation in the SN. On the other hand, the rotenone model was more suitable for studying the role of mitochondrial dysfunction (deficient complex I activity) and Lewy body formation in the SN, which is a characteristic pathological feature of PD. The results indicated that MPTP and rotenone PD models have advantages and disadvantages, therefore one or both should be selected based on the purpose of the study.
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  • 文章类型: Journal Article
    慢性疼痛是主要的健康和社会经济问题,并且存在对持久镇痛药的未满足的需求。SNARE(可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体)是神经肽释放和有害信号转导表面运输所必需的,因此,在外周感觉神经元中选择性表达肉毒神经毒素A(LCA)的SNARE切割轻链蛋白酶可以缓解慢性疼痛。然而,这种方法的安全性问题是缺乏防止LCA在中枢神经系统中表达的感觉神经元启动子。为此,我们利用Pirt(TRP的磷酸肌醇相互作用调节剂)的独特特性,在外周伤害性神经元中表达。第一次,我们鉴定了Pirt启动子元件,并将其克隆到慢病毒载体中,从而在外周感觉神经元中选择性地驱动转基因表达。Pirt启动子驱动的LCA表达在培养的感觉神经元中产生了SNAP-25的快速和浓度依赖性裂解。此外,疼痛相关基因的转录本(TAC1,速激肽前体1;CALCB,降钙素基因相关肽2;HTR3A,5-羟色胺受体3A;NPY2R,神经肽Y受体Y2;GPR52,G蛋白偶联受体52;SCN9A,钠电压门控通道α亚基9;TRPV1和TRPA1,瞬时受体电位阳离子通道亚家族V成员1和亚家族A成员1)在促炎细胞因子刺激的感觉神经元中被病毒介导的LCA表达下调。此外,LCA的病毒表达产生了对疼痛介质释放的持久抑制。因此,我们表明,工程Pirt-LCA病毒可能为长期缓解疼痛提供新的手段。
    Chronic pain is a leading health and socioeconomic problem and an unmet need exists for long-lasting analgesics. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are required for neuropeptide release and noxious signal transducer surface trafficking, thus, selective expression of the SNARE-cleaving light-chain protease of botulinum neurotoxin A (LCA) in peripheral sensory neurons could alleviate chronic pain. However, a safety concern to this approach is the lack of a sensory neuronal promoter to prevent the expression of LCA in the central nervous system. Towards this, we exploit the unique characteristics of Pirt (phosphoinositide-interacting regulator of TRP), which is expressed in peripheral nociceptive neurons. For the first time, we identified a Pirt promoter element and cloned it into a lentiviral vector driving transgene expression selectively in peripheral sensory neurons. Pirt promoter driven-LCA expression yielded rapid and concentration-dependent cleavage of SNAP-25 in cultured sensory neurons. Moreover, the transcripts of pain-related genes (TAC1, tachykinin precursor 1; CALCB, calcitonin gene-related peptide 2; HTR3A, 5-hydroxytryptamine receptor 3A; NPY2R, neuropeptide Y receptor Y2; GPR52, G protein-coupled receptor 52; SCN9A, sodium voltage-gated channel alpha subunit 9; TRPV1 and TRPA1, transient receptor potential cation channel subfamily V member 1 and subfamily A member 1) in pro-inflammatory cytokines stimulated sensory neurons were downregulated by viral mediated expression of LCA. Furthermore, viral expression of LCA yielded long-lasting inhibition of pain mediator release. Thus, we show that the engineered Pirt-LCA virus may provide a novel means for long lasting pain relief.
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