表没食子儿茶素没食子酸酯调控自噬抗心肌缺血再灌注损伤

目的研究表没食子儿茶素没食子酸酯(EGCG)调控自噬抗心肌缺血再灌注损伤的作用。方法64只SD大鼠随机分为假手术、模型、3-甲基腺嘌呤(3-MA,15 mg·kg-1)、EGCG(20 mg·kg-1)四组(n=8),各组于造模前20 min舌下静脉给予相应试剂,采用左冠状动脉前降支结扎法制备大鼠心肌缺血再灌注模型,按试剂盒说明书检测缺血30 min及缺血30 min-再灌注1 h各组肌酸激酶同工酶(CK-MB)、总抗氧化力(T-AOC)、诱导型一氧化氮合酶(i NOS)的含量,以Western-blot法检测心肌微管相关蛋白轻链3蛋白-Ⅱ(LC3-Ⅱ)、Beclin-1、雷帕霉素靶蛋白(m TOR)的表达。结果自噬在心肌缺血期即发生,再灌注时进一步加强;与模型组相比,EGCG组心肌缺血-再灌注不同时段的T-AOC能有效提高,CK-MB及i NOS的含量降低,LC3-Ⅱ、Beclin-1蛋白表达下调,m TOR蛋白表达上调(P<0.05);与3-MA组相比,EGCG组大鼠血清i NOS及CK-MB降低,T-AOC含量提高,LC3-Ⅱ、Beclin-1蛋白表达下调,m TOR蛋白量上调(P<0.05)。结论 EGCG对心肌的保护作用可能与提高抗氧化力,降低i NOS有关;EGCG预处理可能通过短暂诱导心肌缺血期自噬发生,抑制再灌注时段自噬过度表达而减轻心肌缺血再灌注损伤。     

下调 HER2 降低自噬活性抑制人肺癌细胞增殖 转移作用的体外研究

目的 探讨下调 HER2 表达是否抑制细胞自噬活性, 从而影响人肺癌细胞的增殖、 迁徙和侵袭。方法 采用浓度 5 μmol/L 自噬抑制剂 3-MA、 10 μmol/L HER2 抑制剂 Neratinib 分别作用人肺癌细胞 A549。Western blot 检测肺癌细胞 A549 中 HER2、 Beclin-1 及 LC3B （Ⅱ/Ⅰ） 蛋白表达水平; Wound healing 和 Transwell invasion 实验检测 细胞迁徙、 侵袭能力; 四甲基偶氮唑盐 （MTT） 检测细胞的增殖能力。结果 Neratinib 和自噬抑制剂 （3-MA） 作用 24 h 后, 细胞 HER2、 Beclin-1 及 LC3B（Ⅱ/Ⅰ）蛋白表达水平显著低于阴性对照组; Neratinib、 自噬抑制剂（3-MA）处理组 的细胞增殖、 迁徙和侵袭能力显著低于阴性对照细胞。结论 下调 HER2 能降低人肺癌细胞 A549 的自噬活性并抑 制其增殖、 迁徙和侵袭     

小檗碱对心肌缺血再灌注损伤大鼠线粒体自噬及对PINK1/Parkin通路的影响

目的探讨小檗碱对心肌缺血再灌注损伤大鼠线粒体自噬及PTEN诱导激酶1(PTENinducedputativekinase1,PINK1)/帕金森病蛋白(Parkin)通路的影响。方法建立心肌缺血再灌注损伤大鼠模型,随机分组为模型组、小檗碱低、高剂量(75、150 mg/kg)组,自噬抑制剂三甲基腺嘌呤(3-MA,100 mmol/L)组、小檗碱+3-MA(150 mg/kg+100 mmol/L)组,每组12只,另取12只正常大鼠设为假手术组。分组处理后,超声检测大鼠左室功能,记录左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左心射血分数(LVEF)、左室短轴缩短率(FS);三苯基氯化四氮唑(TTC)染色检测各组大鼠心肌梗死面积,酶联免疫吸附实验(ELISA)检测各组大鼠血清中磷酸肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)水平;HE染色观察大鼠心肌组织病理变化;透射电镜观察心肌细胞超微结构及线粒体自噬并分析线粒体损伤评分;蛋白免疫印迹法检测各组大鼠心肌组织PINK1、Parkin蛋白及微管轻链蛋白3B(LC3B)、线粒体自噬受体p62(p62)、泛素特异性蛋白酶30(USP30)蛋白表达。结果与假手术组比较,模型组大鼠心肌组织病理损伤严重,线粒体肿胀及空泡化损伤较多,线粒体损伤评分、心肌梗死面积、LVEDD、LVESD、CK-MB、cTnI水平及PINK1、Parkin、LC3B、p62蛋白表达升高(P0.05),LVEF及FS、USP30蛋白表达降低(P0.05)。与模型组比较,3-MA组大鼠心肌组织及线粒体病理损伤加重,LVEF、FS、PINK1、Parkin、LC3B、p62蛋白表达降低(P0.05),线粒体损伤评分、心肌梗死面积、LVEDD、LVESD、CK-MB、cTnI水平、USP30蛋白表达升高(P0.05);小檗碱低、高剂量大鼠心肌组织及线粒体病理损伤减轻,LVEF、FS、PINK1、Parkin、LC3B、p62、USP30蛋白表达升高(P0.05),线粒体损伤评分、心肌梗死面积、LVEDD、LVESD、CK-MB、c TnI水平降低(P0.05)。小檗碱+3-MA组大鼠上述各项指标均与小檗碱高剂量组变化趋势相反,且有统计学差异(P0.05)。结论小檗碱可能通过激活PINK1/Parkin/P62/LC3B通路促进线粒体自噬,升高USP30表达,减少异常自噬,缓解心肌缺血再灌注损伤。     

玉郎伞查尔酮调控PI3K/Akt信号通路抗心肌缺血/再灌注损伤的作用及机制研究

目的探讨玉郎伞查尔酮(YLSC)调控PI3K/Akt信号通路抗心肌缺血/再灌注损伤的作用及机制。方法 40只♂SD大鼠随机分为5组:假手术组、模型组、YLSC组、YLSC+PI3K抑制剂wortmannin组(YLSC+WM组)、PI3K抑制剂wortmannin组(WM组),每组8只。除假手术组外,其它各组大鼠均结扎冠状动脉左前降支制备心肌缺血模型,缺血30 min,再灌注120 min。实验结束后,采用比色法测定大鼠血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)及一氧化氮(NO)水平,ELISA法测定血清肿瘤坏死因子(TNF-α)的含量,Western blot法检测心肌组织中总Akt(t-Akt)、磷酸化Akt(p-Akt)及自噬相关蛋白LC3-Ⅱ的表达,FQ-PCR法分析内皮型一氧化氮合酶(eN OS)、凋亡因子caspase-3及自噬相关基因Beclin1的表达量变化。结果与I/R组比较,YLSC组CK-MB、LDH以及TNF-α血清含量明显降低,NO水平升高,Beclin1、caspase-3及LC3-Ⅱ的表达量均明显下降,同时Akt的磷酸化水平与eN OS mR NA表达增加,上述各项指标差异具有统计学意义(P<0.05),而上述变化能够被PI3K/Akt信号通路的特异性阻断剂wortmannin所阻断,且其差异具有统计学意义(P<0.05)。结论 YLSC通过激活PI3K/Akt信号通路抑制缺血/再灌注所致的心肌细胞凋亡和过度自噬,从而发挥对心肌缺血/再灌注损伤的保护作用。     

银杏总黄酮通过调节自噬减轻大鼠心肌缺血再灌注损伤的研究

目的 探讨银杏总黄酮是否可以通过调节自噬减轻心肌缺血再灌注(I/R)损伤以及可能的机制。方法 采用大鼠心肌I/R模型(缺血30 min,再灌注4 h),雄性SD大鼠30只随机分为三组:假手术组(SO组,n=10)、缺血再灌注组(I/R组,n=10)和银杏总黄酮治疗组(YLTF+I/R组,n=10,100 mg·kg-1,造模前灌胃7 d)。检测心肌损伤标记物肌酸激酶(CK)、乳酸脱氢酶(LDH)和肌钙蛋白I(cTnI)；检测氧化应激水平,即丙二醛(MDA)和超氧化物歧化酶(SOD)水平；检测自噬蛋白beclin-1和LC3水平。结果 与SO组比较,I/R可诱导心肌损伤标记物(CK、LDH和cTnI)表达升高,氧化应激水平的增加(MDA表达增加,SOD表达降低)和自噬的过度激活(LC3-Ⅱ/Ⅰ比值增加,beclin-1表达增加)；与I/R比较,银杏总黄酮可显著的降低心肌损伤标记物(CK、LDH和cTnI)的表达、氧化应激水平(MDA表达降低,SOD表达增加)和自噬的过度激活(LC3-Ⅱ/Ⅰ比值降低,beclin-1表达减低)。结论 银杏总黄酮可以通过抑制过度自噬减轻心肌I/R损伤,这可能与其抑制氧化应激作用有关。     

自噬促进大鼠肠缺血再灌注损伤的细胞铁死亡

目的:探讨自噬对肠缺血再灌注损伤中细胞铁死亡的影响。方法:采用随机数字表法将24只SPF级Wistar大鼠(体质量200～220 g)分为4组(n=6):伪手术组(sham组)、缺血组(I组)、缺血再灌注组(I/R组)、缺血再灌注+自噬抑制剂组(I/R+3-MA组)。夹闭肠系膜上动脉1 h构建缺血模型，再灌注2 h建立大鼠肠缺血再灌注损伤模型；采用HE染色光镜下观察肠黏膜病理改变并行Chiu评分；比色法检测Fe²⁺含量；ELISA法检测乳酸脱氢酶(LDH)、过氧化脂质(LPO)含量；Western Blot检测铁蛋白重肽(ferritin heavy polypeptide, FTH)1、核受体共激活子(nuclear receptor coactivator, NCOA)4、LC3-II/I表达，透射电镜检测线粒体形态。结果:与sham组比较，其余3组小肠组织Chiu评分均增高(P<0.01),LC3II/I表达上调，FTH1、NCOA4表达下调(P<0.01),I组、I/R组LDH、Fe²⁺含量升高(P<0.01),I/...     

三氟淫羊藿素对心肌缺血再灌注损伤大鼠Akt/mTOR信号通路及自噬相关蛋白水平的影响

目的研究三氟淫羊藿素(ICTF)对大鼠心肌缺血再灌注损伤(MI/RI)的治疗作用,并探讨其是否通过丝氨酸/苏氨酸蛋白激酶/哺乳动物雷帕霉素靶蛋白(Akt/mTOR)信号通路调节自噬起作用。方法采用结扎左冠状动脉前降支45 min,再灌注60 min的方法制作MI/RI模型,雄性SD大鼠分为假手术组、MI/RI模型组、ICTF 0.5,1.0和2.0 mg·kg~(-1)组。标准肢体Ⅱ导联心电图监测T波和ST段变化,TTC染色测定心肌梗死面积,Western印迹法检测心肌组织中微管相关蛋白2/1轻链3(LC3Ⅱ/LC3Ⅰ)比值、Akt和mTOR蛋白磷酸化水平,免疫荧光检测心肌组织LC3蛋白表达水平。结果监测心电图发现,与假手术组相比,MI/RI模型组大鼠再灌注60 min时的T波(P<0.05)和ST段(P<0.01)明显升高;与模型组相比,ICTF 1.0 mg·kg~(-1)组的T波(P<0.05)和ST段(P<0.01)显著降低。TTC染色结果表明,模型组出现明显的心肌梗死灶(P<0.01),ICTF 1.0 mg·kg~(-1)组心肌梗死面积百分数显著降低(P<0.01)。Western印迹结果显示,与假手术组比较,模型组LC3Ⅱ/LC3Ⅰ比值显著升高(P<0.01),Beclin~(-1)蛋白磷酸化水平升高(P<0.05),Akt(P<0.01)和m TOR(P<0.05)蛋白磷酸化水平降低;与模型组相比,ICTF 1.0 mg·kg~(-1)组LC3Ⅱ/LC3Ⅰ比值明显降低(P<0.01),Beclin~(-1)(P<0.01)蛋白磷酸化水平降低,Akt和m TOR蛋白磷酸化水平升高(P<0.01)。免疫荧光结果表明,与假手术组相比,模型组大鼠心肌组织中LC3蛋白表达增多(P<0.01);与模型组比较,ICTF 1.0 mg·kg~(-1)组表达减少(P<0.01)。结论 ICTF对大鼠MI/RI具有保护作用,其机制可能与调控Akt/m TOR信号通路抑制细胞过度自噬有关。     

土槿乙酸诱导的卵巢癌细胞HO-8910自噬及其机制

目的探讨土槿乙酸诱导的人卵巢癌细胞系HO-8910细胞自噬蛋白的表达及PI3K/Akt信号转导通路的变化,以及自噬特异性抑制剂3-甲基腺嘌呤(3-MA)和自噬激动剂雷帕霉素(RAPA)对自噬相关蛋白的影响。方法不同浓度的土槿乙酸作用HO-8910细胞,采用台盼蓝染色检测细胞的存活率,Western blot分析检测自噬相关蛋白及PI3K/Akt通路相关蛋白的变化,分别用3-MA和RAPA处理HO-8910细胞后检测自噬相关蛋白的变化。结果土槿乙酸能够诱导卵巢癌细胞HO-8910自噬,增加LC3-Ⅱ和自噬调节因子Beclin-1的表达;3-MA可以抑制土槿乙酸诱导的HO-8910细胞自噬相关蛋白的表达,而RAPA促进了土槿乙酸诱导的HO-8910细胞自噬相关蛋白的表达,且土槿乙酸能抑制PI3K/Akt通路蛋白的表达。结论土槿乙酸可通过抑制PI3K/Akt通路诱导HO-8910细胞自噬。     

二氢杨梅素通过上调自噬活性抑制MPP~+诱导的PC12细胞损伤

目的观察二氢杨梅素(DMY)对1-甲基-4-苯基吡啶离子(MPP+)诱导的PC12细胞损伤的影响并探讨其可能的机制。方法含DMY 5,10,20,40和80μmol·L~(-1)的培养液预处理PC12细胞0.5 h,培养液中加入自噬抑制剂3-甲基腺嘌呤(3-MA)10 mmol·L~(-1),再加入MPP+500μmol·L~(-1)培养48 h。噻唑蓝(MTT)法检测细胞存活,丙酮酸二硝基苯腙比色法检测细胞培养液中乳酸脱氢酶(LDH)水平,透射电镜观察细胞的超微结构,Western蛋白质印迹法检测细胞中自噬相关蛋白Beclin-1和微管相关蛋白1轻链3(LC3)和P62的表达。结果与细胞对照组比较,MPP+组细胞存活率显著降低(P<0.05),细胞培养液中LDH水平显著增加(P<0.05),细胞中自噬体的数量明显减少,自噬泡占胞质总面积的百分率显著降低(P<0.05),LC3-Ⅱ和Beclin-1的蛋白表达及LC3-Ⅱ/LC3-Ⅰ的比值均显著降低(均P<0.05),P62的表达显著升高(P<0.05)。与MPP+组比较,MPP++DMY 10~80μmol·L~(-1)组细胞存活率显著升高(P<0.05),细胞培养液中LDH水平显著降低(P<0.05)。与MPP+组比较,MPP++DMY 20μmol·L~(-1)组细胞中自噬体数量明显增加,自噬泡占胞质总面积的百分率显著增加(P<0.05),LC3-Ⅱ和Beclin-1的蛋白表达和LC3-Ⅱ/LC3-Ⅰ的比值均显著增加(P<0.05),P62的表达显著降低(P<0.05)。与MPP++DMY 20μmol·L~(-1)组比较,MPP++DMY+3-MA组细胞存活率显著降低(P<0.05),细胞上清液中LDH水平显著增加(P<0.05)。结论 DMY抑制MPP+诱导的PC12细胞损伤,其机制与上调细胞自噬活性有关。     

雷公藤甲素诱导自噬促进人肾小管上皮HK-2细胞凋亡

目的 研究自噬在雷公藤甲素(triptolide, TP)诱导人肾近端小管上皮HK-2细胞凋亡中的作用。方法 以HK-2细胞为研究对象,CCK-8法检测细胞存活率;倒置荧光显微镜观察细胞形态变化;流式细胞术检测细胞凋亡率和线粒体膜电位MMP变化;激光扫描共聚焦显微镜观察细胞内LC3荧光强度变化;Western blot检测细胞凋亡及自噬相关蛋白cleaved caspase 9、caspase 9、Bax、Bcl-2、LC3、p62和Beclin 1的表达;采用自噬抑制剂3-甲基腺嘌呤(3-methyladenine, 3-MA)和自噬激动剂雷帕霉素(rapamycin, Rap)研究自噬对TP诱导HK-2细胞凋亡的影响。结果 TP降低HK-2细胞存活率,诱导细胞凋亡和自噬,降低MMP水平,增加胞内LC3Ⅱ荧光强度,上调Beclin 1表达,下调p62表达,升高cleaved caspase 9/caspase 9、Bax/Bcl-2和LC3Ⅱ/LC3Ⅰ比值。此外,与TP组相比,3-MA+TP组细胞内LC3Ⅱ/LC3Ⅰ和cleaved caspase 9/caspase 9比值降低,p...     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.