Explore the vast range of titles available.

目的探讨β-分泌酶底物肽（BACEsp）对阿尔茨海默病（AD）细胞模型保护作用的机制。方法用携带BAC-Esp基因的重组病毒pLXSN-BACEsp（pBV）,作用经淀粉样前体蛋白（APP）转染SK-N-SH细胞建立的AD细胞模型。MTT法检测细胞的活性,免疫细胞化学方法观察BACEsp作用前、后细胞内APP表达量的变化。结果pBV预处理组细胞的活性、胞内APP的表达量显著高于AD模型组和pBV后处理组。结论BACEsp对由APP所造成的AD细胞模型的神经毒性具有明显的保护作用。

目的 研究造模时间及免疫次数对促甲状腺激素受体（TSHR）A亚单位的重组腺病毒（Ad-TSHR289）诱导的毒性弥漫性甲状腺肿（Graves病）模型的影响.方法45只BALB/c小鼠分别注射对照腺病毒（Ad-Lacz）或Ad-TSHR289,于第2次免疫后2周或第3次免疫后4周处死.所有小鼠均采取摘眼球取血,放免法检测血清促甲状腺激素受体抗体（TRAb）以及总甲状腺素（TT4）水平;剥离甲状腺,进行组织学检查.结果 所有注射Ad-TSHR289的小鼠相对于对照组TRAb均明显升高;5周-造模组、10周-造模组的Graves病发病率分别为56%（9/16）、75%（9/12）;10周-造模组甲状腺组织学改变与TT4水平变化吻合度为100%,相对于5周-造模组的50%（8/16）明显升高.结论 10周-造模组相对于5周-造模组具有发病率高、组织学改变与血清TT4水平吻合度高等优势;造模时间以及免疫次数均对该Graves病模型有着较大的影响.

Alzheimer＇s disease （AD） is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress （OS） and tauopathy is believed to be one of the major players in AD development. Here, we demonstrated the capability of the small molecule N-（1,3-benzodioxol-5-yl）-2-[5-chloro-2- methoxy（phenylsulfonyl）anilino]acetamide （LX2343） to ameliorate the cognitive dysfunction of AD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy. Streptozotocin （STZ） was used to induce OS in neuronal cells in vitro and in AD model rats that were made by intracerebroventricular injection of STZ （3 mg/kg, bilaterally）, and Morris water maze test was used to evaluate the cognitive dysfunction in ICV-STZ rats. Treatment with LX2343 （5-20 pmol/L） significantly attenuated STZ-induced apoptosis in SH-SY5Y cells and mouse primary cortical neurons by alleviating OS and inhibiting the JNK/p38 and pro-apoptotic pathways. LX2343 was able to restore the integrity of mitochondrial function and morphology, increase ATP biosynthesis, and reduce ROS accumulation in the neuronal cells. In addition, LX2343 was found to be a non-ATP competitive GSK-3β inhibitor with ICso of 1.84＋0.07 pmol/L, and it potently inhibited tau hyperphosphorylation in the neuronal cells. In ICV-STZ rats, administration of LX2343 （7, 21 mg·kg^-1·d^-1, ip, for 5 weeks） efficiently improved their cognitive deficits. LX2343 ameliorates the cognitive dysfunction in the AD model rats by suppressing OS-induced neuronal apoptosis and tauopathy, thus highlighting the potential of LX2343 for the treatment of AD.

Dysregulation of β-site APP-cleaving enzyme （BACE） and/or γ-secretase leads to anomalous production of amyloid-β peptide （Aβ） and contributes to the etiology of Alzheimer＇s disease （AD）. Since these secretases mediate proteolytic processing of numerous proteins, little success has been achieved to treat AD by secretase inhibitors because of inevitable undesired side effects. Thus, it is of importance to unravel the regulatory mechanisms of these secretases. Here, we show that δ-opioid receptor （DOR） promotes the processing of Aβ precursor protein （APP） by BACE1 and γ-secretase, but not that of Notch, N-cadherin or APLP. Further investigation reveals that DOR forms a complex with BACE1 and γ-seeretase, and activation of DOR mediates the co-endocytic sorting of the secretases/ receptor complex for APP endoproteolysis. Dysfunction of the receptor retards the endocytosis of BACE1 and γ-secretase and thus the production of Aβ Consistently, knockdown or antagonization of DOR reduces secretase activities and ameliorates Aβ pathology and Aβ-dependent behavioral deficits, but does not affect the processing of Notch, N-cadherin or APLP in AD model mice. Our study not only uncovers a molecular mechanism for the formation of a DOR/secretase complex that regulates the specificity of secretase for Aβ production but also suggests that intervention of either formation or trafficking of the GPCR/secretase complex could lead to a new strategy against AD, potentially with fewer side effects.

Type 2 diabetes （T2D） is an important risk factor for developing dementias, including Alzheimer＇s disease （AD）. Hyperinsulin- emia and glucose intolerance, as features of T2D, might increase the neurodegeneration process, synaptic loss and brain atrophy, leading to cognitive impairment observed in AD. Also, adult neurogenesis seems to be impaired in AD models. Therefore, we have studied morphological alterations, cell proliferation and neurogenesis in the central nervous system （CNS） from a classical model of T2D, the db/db mouse, and in a prediabetes insulin-resistant model, obtained after long-term high fat diet （HFD） administration to C57B1/6 mice. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. Neurogen- esis and cell proliferation were increased in young db/db mice, when compared with control mice, whereas no differences were detected in the prediabetic model. We also detected significant correlations between metabolic parameters and central atrophy, altered proliferation and neurogenesis in the central nervous system. Altogether these data support that glycaemia control in elderly patients, could help to control central alterations and improve dementia prognosis.