Adaptive Simulated Annealing Based Protein Loop Modeling of Neurotoxins

A loop modeling method, adaptive simulated annealing, for ab initio prediction of protein loop structures, as an optimization problem of searching the global minimum of a given energy function, is proposed. An interface-friendly toolbox—LoopModeller in Windows and Linux systems, VC++ and OpenGL environments is developed for analysis and visualization. Simulation results of three short-chain neurotoxins modeled by LoopModeller show that the method proposed is fast and efficient.

Genomic,transcriptomic,and epigenomic analysis of a medicinal snake,Bungarus multicinctus,to provides insights into the origin of Elapidae neurotoxins

The many-banded krait,Bungarus multicinctus,has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia.Characterization of its venoms classified chief phyla of modern animal neurotoxins.However,the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome.Here,we present the 1.58 Gbp genome of B.multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp.Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications.The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins(3FTxs)from membrane tethering before the Colubroidea divergence.Subsequent expansion and mutations diversified and recruited these 3FTxs.After the cobra/krait divergence,the modern unit-B ofβ-bungarotoxin emerged with an extra cysteine residue.A subsequent point substitution in unit-A enabled theβ-bungarotoxin covalent linkage.The B.multicinctus gene expression,chromatin topological organization,and histone modification characteristics were featured by transcriptome,proteome,chromatin conformation capture sequencing,and ChIP-seq.The results highlighted that venom production was under a sophisticated regulation.Our findings provide new insights into snake neurotoxin research,meanwhile will facilitate antivenom development,toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxins

Diverse subtypes of voltage-gated sodium channels(VGSCs)have been found throughout tissues of the brain,muscles and the heart.Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch(BmK)act as sodium channel-specific modulators and have therefore been widely used to study VGSCs.α-type neurotoxins,named BmK I,BmKαIV and BmK abT,bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs.In contrast,β-type neurotoxins,named BmK AS,BmK AS-1,BmK IT and BmK IT2,occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels.Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs,however,indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simpleα-type and β-type neurotoxin distinction.Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region-and/or speciesspecific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs.In this review,we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3-or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.

Molecular Characteristics of Four New Depressant Insect Neurotoxins Purified From Venom of Buthus martensi Karsch by HPLC

Suitable pattern and high yield were obtained when the reverse-phase performance liquidchromatography (RP-HPLC) was used to separate neurotoxins from venom of Chinese scorpion Buthusmartensi Karsch.Using this technique,the venom was first separated to two main regions.The toxicitytests show that the insect-selective neurotoxical components are concentrated in the latter region,from whichfive insect-selective neurotoxins designated by BmK IT1-IT5 were obtained.According to the results of thetoxicity test as well as the amino acid composition and N-terminal analyses,BmK IT1 is the excitatory insectneurotoxin as reported in a previous paper,and the others are the newly found depressant insect-selectiveneurotoxins.The molecules of all the four toxins are single-chain minipeptides of about 60 amino acids.Their isoelectric points (pI) are between 8.3 and 8.5.The fact that BmK IT2 loses completely its insect tox-icity after being modified by fluorochrome shows that the positive charges on the molecular surface of thiskind of toxins are important to maintaining the bioactivity of the molecules.

Security breach:peripheral nerves provide unrestricted access for toxin delivery into the central nervous system

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport.This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis.We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.

Relative Molecular Similarity in Compound Structures Modulating Neurodegenerative Apoptosis

Neurodegeneration is attributable to metabolic disturbances in the various cell types responsible for this condition, in respect of glucose utilisation and dysfunctional mitochondrial oxidative mechanisms. The properties of neurotoxins and antagonists that limit their action are well documented in disease models, whereas effective therapy is very limited. Cell apoptosis, a general marker of neurodegeneration, is also of therapeutic interest in the treatment of cancer. cGMP nucleotide influences apoptosis and has a role in maintaining equilibrium within cell redox parameters. The chemical structure of cGMP provides a comparative template for demonstrating relative molecular similarity within the structures of natural and synthetic compounds influencing tumour cell apoptosis. The present study uses computational software to investigate molecular similarity within the structures of cGMP and compounds that modulate cell apoptosis in experimental models of diabetic peripheral neuropathy (DPN), Parkinson’s and multiple sclerosis. Differential molecular similarity demonstrated in neurotoxin and antagonist structures implicate metabolite impairment of cGMP signaling function as a common mechanism in the initial phases of these neurodegenerative conditions.

Isolation and characterization of Hainantoxin-II, a new neurotoxic peptide from the Chinese bird spider (Haplopelma hainanum)

Hainantoxin-II （HnTx-II）, a novel neurotoxin, was isolated from the venom of the Chinese bird spider （Haplopelma hainanum） by cation exchange chromatography and reverse-phase HPLC. The toxin was a single chain polypeptide with calculated molecular weight of 4 253.135 obtained by mass spectrometry. The complete amino acid sequence of HnTx-II was determined by Edman degradation and found to contain 37 residues with three disulfide bonds. Results showed HnTx-II can reversibly paralyze cockroaches for several hours after intra-abdominal injection with ED50 of 16 μg/g and kill the insects immediately at a dose of 60 μg/g. It was also shown to kill mice at a LD50 value of 1.41μg/g after intracerebroventricular injection. Hainantoxin-II shares 91% sequence homology with Huwentoxin-II （HwTx-II）, an insecticidal peptide from another bird spider （Haplopelma schmidti） with a unique scaffold. While HnTx-II and HwTx-II both exhibit toxic activities in insects and mammals, HnTx-II shows higher insecticidal activity and lower lethiferous activity of mammals than HwTx-II. These results help clarify structural-functional relationships of the polypeptide toxin.

Fungal-contaminated grass and well water and sporadic amyotrophic lateral sclerosis

Fungi are important infectious disease-causing agents,but are often overlooked as environmental factors in disease.We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic lateral sclerosis(ALS),the most common form of motor neurone disease.Approximately 90%cases of ALS are sporadic,and the aetiology of sporadic ALS is still unknown.We have previously postulated that grass or soil-associated fungal infections may be a leading cause of sporadic ALS.Herein we extend this proposal to water-associated fungi.A wide variety of fungi have been reported in drinking water including Acremonium,Alternaria,Aspergillus,Cladosporium,Fusarium,Penicillium and Trichoderma.Some of these are known to produce neurotoxic mycotoxins.Despite this,drinking water is not routinely monitored for fungal contamination.Fungal contamination could explain the close correlation between distribution of well water and cases of sporadic ALS in the United States.We propose several mechanisms by which an opportunistic fungal infection from environmental exposure(to water,soil or plants)can lead to long term neuronal degradation resulting in the hallmarks of ALS.If confirmed,the association between fungal infection and sporadic ALS could lead to novel treatment strategies for this progressive and fatal disease.

Successful treatment of encrusted cystitis:A case report and review of literature

BACKGROUND Encrusted cystitis(EC)is a chronic inflammation of the bladder associated with mucosal encrustations.Early diagnosis and optimal treatment are not well established.Here,we report a case of EC successfully treated with com-bination therapy.CASE SUMMARY A 27-year-old man presented with frequency,urgency,dysuria,gross hematuria and suprapubic pain for 2 mo.He was diagnosed with EC based on characteristic calcifications of the bladder wall(most of them were struvite),cystoscopy and histopathological examination.He was cured after combined therapy of elimination of encrustations,bladder instillation of hyaluronic acid and injection of botulinum-A neurotoxin into bladder submucosal tissue.CONCLUSION Bladder instillation of hyaluronic acid and injection of botulinum-A neurotoxin into the bladder submucosal tissue can be used for treatment of EC.

HPLC Determination of Neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid and Its α -Isomer in Lathyrus sativus by Precolumn Derivatisation with 1-Fluoro-2,4-dinitrobenzcne

A rapid and simple method is presented for determining β-N-oxalyl-α. β- diaminopropionic acid (β -ODAP) and its much less toxic α -isomer (α -ODAP) in Lathyrus sativus. Seed and foliage extracts of Lathyrus sativus were treated with 1-fluoro-2,4-dinitrobenzene (FDNB) and a reversed-phase high-performance liquid chromatographic method for the separation of the derivatives in the pmol range is reported.

Novel Kunitz-like peptides discovered in zoanthid Palythoa caribaeorum through transcriptome sequencing

OBJECTIVE Palythoa caribaeorum(class Anthozoa) is a zoanthid that together jellyfishes,hydra,and sea anemones,which are venomous and predatory,belongs to the Phyllum Cnidaria.The distinguished feature in these marine animals is the cnidocytes in the body tissues,responsible for toxin production and injection that are used majorly for prey capture and defense.With exception for other anthozoans,the toxin cocktails of zoanthids have been scarcely studied and are poorly known.METHODS Based on the analysis of P.caribaeorum transcriptome,numerous predicted venom-featured polypeptides were identified,including allergens,neuro-toxins,membrane-active and Kunitz-like peptides(PcKuz).The three predicted PcKuz isotoxins(1 to 3) were selected for functional studies.Through computational processing comprising structural phylogenetic analysis,molecular docking,and dynamics simulation,PcKuz3 was shown to be a potential voltage gated potassium-channel inhibitor.RESULTS PcKuz3 fitted well as new functional Kunitz-type toxins with strong anti-locomotor activity as in vivo assessed in zebrafish larvae,with weak inhibitory effect toward proteases,as evaluated in vitro.Notably,PcKuz3 can suppress,at low concentration,the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish,which indicated PcKuz3 may have a neuroprotective effect.CONCLUSION Taken together,PcK uz3 figures as a novel neurotoxin structure which differs from known homologous peptides expressed in sea anemone.Moreover,the novel PcKuz3 provides an insightful hint for bio-drug development for prospective neurodegenerative disease treatment.

The microstructural effects of aqueous extract of Garcinia kola(Linn) on the hippocampus and cerebellum of malnourished mice

Objective:To assess the neuroprotective effects of aqueous extract of Garcinia kola on neurotoxin administered malnourished mice adopting histological procedure.Methods:The study was carried out using thirty-two adult malnourished mice which were randomly assigned into four groups(n=8):A,B,C and D.Group A served as control,while the other groups served as the experimental groups.Animals in group A were fed malnourished diet ad libitum and given water liberally.Animals in group B were administered with 3-Nitropropionic acid(3-NP)(neurotoxin)only at 20 rag/kg body weight,group C were given only Garcinia kola extracts,and group D were pre-treated with Garcinia kola extracts at 200 mg/kg for seven days prior to administration of neurotoxin at 20 mg/kg body weight.After three days of neurotoxins administration in the relevant groups,the brains were excised and fixed in formal calcium for histological processing.Results:The study showed that hippocampal and cerebellar neurons of animals in group B exhibited some cellular degeneration and blood vessel blockage,which were not seen in groups A,C and D.Cresyl violet staining was least intense in group B than in groups A,C and D.Despite the fact that animals in group D has equal administration of 3-Nitropropionic acid concentration,there were no traces of neural degeneration as it was evidenced in group B.Conclusions:It is concluded that Garcinia kola has protective effects on the neurons of the hippocampus and cerebellum of malnourished mice.

Eosinophil associated genes in the inflammatory bowel disease 4 region:Correlation to inflammatory bowel disease revealed

AIM： To study the association between inflammatory bowel disease （IBD） and genetic variations in eosinophil protein X （EPX） and eosinophil cationic protein （ECP）. METHODS： DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn＇s disease （CD）, 592 with ulcerative colitis （UC） and 300 healthy subjects. The EPX405 （G 〉 C, rs2013109）, ECP434 （G 〉 C, rs2073342） and ECP562 （G 〉 C, rs2233860） gene polymorphisms were analysed, by the 5＇-nuclease allelic discrimination assay. For de- termination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylam- monium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent as- say. The intracellular content of ECP was analysed with the UniCAP system as described by the manufacturer. Statistical tests for calculations of results were χ2 test, Fisher＇s exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P 〈 0.05 were considered statistically significant.RESULTS： The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years （n = 57） was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject＇s genotype frequencies of ECP434 （GG = 57%, GC = 38%, CC = 5%; P = 0.010） and ECP562 （GG = 68%, GC = 29%,CC = 3%; P = 0.009）. The genotype frequencies for females, with an age of dis- ease onset of ≥ 45 years with CD （n = 62）, was for the ECP434 and ECP562 genotypes GG = 37%, GC =52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 （P = 0.010） and ECP562 （P = 0.013）. The intracellular protein concen- tration of EPX and ECP was calculated in μg/10^6 eosi- nophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 （GG = 4.65, GC = 5.93, and CC = 6.57） and for ECP in the patients with the GG genotype of EPX405 （GG = 2.70, GC = 2.47 and CC = 1.90）. ANOVA test demonstrated a difference in intracellular protein content for EPX （P = 0.009） and ECP （P = 0.022）. The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference be- tween haplotype distributions for the females with CD （P = 0.003）. The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype （34 years） and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype （21 years）. For males with UC there was also a difference between the highest and lowest age of the disease on- set （EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009）. The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dys- plasia/cancer was 2.5 （95%CI： 1.2-5.4, P = 0.01） and 2.5 （95%CI： 1.1-5.4, P = 0.02） respectively, compared to patients carrying the GG-genotypes.

Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis induced by rotenone and 6-hydroxydopamine

It has been well documented that Achyranthes bidentata polypeptides（ABPPs） are potent neuroprotective agents in several types of neurons. However, whether ABPPs protect dopaminergic neurons from apoptosis induced by neurotoxins is still unknown. This study was designed to observe the effect of ABPPk, a purified fraction of ABPPs, on apoptosis of dopaminergic neurons. SH-5YHY cells and primary dopaminergic neurons were pre-treated with ABPPk（25, 50, or 100 ng/mL） for 12 hours. Cells were then exposed to 6-hydroxydopamine（50 or 150 μM） or rotenone（50 or 200 μM） for 36 hours to induce cell apoptosis. Our results demonstrate that ABPPk markedly increased viability in SH-SY5Y cells and primary dopaminergic neurons, decreased lactate dehydrogenase activity and number of apoptotic dopaminergic neurons, elevated mitochondrial membrane potential, and increased Bcl-2/Bax ratio. These findings suggest that ABPPk protects dopaminergic neurons from apoptosis, and that ABPPk treatment might be an effective intervention for treating dopaminergic neuronal loss associated with disorders such as Parkinson＇s disease.

S-methyl-L-cysteine Protects against Antimycin A-induced Mitochondrial Dysfunction in Neural Cells via Mimicking Endogenous Methionine-centered Redox Cycle

Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration.Mitochondria-targeted antioxidants,such as MitoQ,have emerged as potentially effective antioxidant therapies.Methionine sulfoxide reductase A(MsrA)is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine(Met)-centered redox cycle(MCRC).In this study,we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells.This antioxidation was largely dependent on the Met oxidase activity of MsrA.S-methyl-L-cysteine(SMLC),a natural analogue of Met that is abundantly found in garlic and cabbage,could activate the Met oxidase activity of MsrA to scavenge free radicals.Furthermore,SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium(MPP+)-induced neurotoxicity.Thus,our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.

Polyclonal antibody against an insect excitatory toxin BmKIT from Buthus Martensii karsch and detection of BmKIT expressed in transgenic cotton

An insect excitatory toxin gene from Buthus martensii Karseh （BmKIT） was cloned into the expression vector, pET-28a. BmKIT was expressed as inclusion bodies in Eseherichia coli BL21 （DE3） host cells. The authenticity of in vitro expressed protein was confirmed by Western blot. The inclusion body protein band in SDS-PAGE was excised and the protein, BmKIT, was extracted. Polyelonal antibodies to the purified protein were raised in rabbits. The antibody reacted specifically with the expressed BmKIT and was used to quantify its presence in transgenic cotton.

Mechanism of mitochondrial protection by the Buyin Qianzheng formula in a Parkin overexpression cell model

Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula(BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease(PD)cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion(MPPþ).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate(ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mitochondrial morphology,activity,and mitochondrial membrane potential(DJm).Western blot was conducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynaminrelated protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPPþ-induced mitochondrial damage,increased mitochondrial activity and DJm.BYQZF increased the survival of MPPþ-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the DJm and ATP levels.These findings suggested that BYQZF protected against MPPþ-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1(closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamicrelated protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPPþ-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS

Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.

Latest Advances in the Treatment of Post-stroke Limb Spasm with Botulinum Neurotoxin

Objective: To describe the latest progress in the use of botulinum neurotoxin for post-stroke limb spasm. Methods: This paper looks up the relevant research literatures in recent years in PubMed, Web of Science, Springer, Ovid, CNKI, WanFang databases and summarizes them. Results: The latest progress in the use of botulinum neurotoxin for post-stroke limb spasm was studied from the following aspects: the action mechanism of botulinum neurotoxin;efficacy evaluation;injection dose;target muscle selection;guiding technology;combination therapy. Conclusion: Botulinum neurotoxin is the first-line treatment for post-stroke limb spasm. We need to make continuous improvement and progress from the treatment period, injection dose, target muscle selection, guiding technology and efficacy evaluation to improve the quality of life of the majority of post-stroke survivors in China.