The role of apoptosis-related proteins in pathological changes of Alzhei-mer′s disease
WEN Shirong1 YU Yanhong2 WANG Desheng1 WANG Chunli1 LI Xuling3 YANG Hui3
1.Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin 150001, China;
2.Department of Neurology, Shandong Provincial Third Hospital, Shandong Province, Ji′nan 250031, China;
3.Department of Neurology, the Fourth Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin 150001, China
Abstract：Objective To study the role of apoptosis-related proteins in pathological changes of Alzheimer′s disease. Methods Six senescence accelerated mouse P8 (SAMP8) aged 3 months, 12 SAMP8 aged 6 months and 6 senescence accelerated mouse/resistance 1 (SAMR1) aged 6 months were selected and divided into four groups, group A had 6 SAMR1 mice of 6-month-old, group B had 6 SAMP8 mice of 3-month-old, both groups were selected as control. Group C had 6 SAMP8 mice (sham treatment group), Group O had 6 SAMP8 mice (drug treatment group) aged 6 months. Group O was intraperitoneally injected with Obatoclax 0.2 mL, while group C was injected with the same amount of 0.9% physiological saline for 14 consecutive days. The cognitive function was tested by Morris water maze and the levels of Bcl-2, p-tau and caspase-3 were detected by immunohistochemistry. Results Compared with group A, the incubation periods of Morris water maze experiment in group B, C and O were significantly prolonged, and the times of platform crossings were significantly reduced (P < 0.05). Compared with the first experiment, the incubation period of the second Morris water maze experiment in group O was highly prolonged, and the times of platform crossings was statistically decreased (P < 0.05). Compared with group C, the number of positive cells protein of Bcl-2 in group O increased significantly (P < 0.05), but there was no significant difference in the mean optical density (IOD) and number of positive cells of caspase-3 (P > 0.05), there also was no significant difference in the IOD and number of positive cells of p-tau protein (P > 0.05). Conclusion The SAMP8 mice show a tendency of memory decline with prolonged survival time. Bcl-2 is a key component in cognitive change and cognitive change may not through pathways of the caspase-3 or p-tau.
温世荣1 于艳红2 王德生1 王春利1 李绪领3 杨慧3. 凋亡相关蛋白在阿尔茨海默病病理改变中的作用[J]. 中国医药导报, 2019, 16(25): 16-19.
WEN Shirong1 YU Yanhong2 WANG Desheng1 WANG Chunli1 LI Xuling3 YANG Hui3. The role of apoptosis-related proteins in pathological changes of Alzhei-mer′s disease. 中国医药导报, 2019, 16(25): 16-19.
[1] Miao J，Shi R，Li L，et al. Pathological tau from Alzheimer′s brain induces site-specific hyperphosphorylation and SDS- and reducing agent-resistant aggregation of tau in vivo [J]. Front Aging Neurosci，2019，11：34-47.
[2] Fath T，Eidenmuller J，Brandt R，et al. Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzhei-mer′s disease [J]. J Neurosci，2002，22（22）：9733-9741.
[3] Saha P，Sen N. Tauopathy：A common mechanism for neurodegeneration and brain aging [J]. Mech Ageing Dev，2019，178：72-79.
[4] Shimada A，Hasegawa-Ishii S. Senescence-accelerated mice（SAMs）as a model for brain aging and immunosenescence [J]. Aging Dis，2011，2（5）：414-436.
[5] Farr SA，Roesler E，Niehoff ML，et al. Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer′s disease [J]. J Alzheimers Dis，2019，68（4）：1699-1710.
[6] Wen H，Fu Z，Wei Y，et al. Antioxidant activity and neuroprotective activity of stilbenoids in rat primary cortex neurons via the PI3K/Akt signalling pathway [J]. Molecules，2018，23（9）：2328-2342.
[7] Obulesu M，Lakshmi MJ. Apoptosis in Alzheimer′s disease：an understanding of the physiology，pathology and therapeutic avenues [J]. Neurochem Res，2014，39（12）：2301-2312.
[8] Chang CC，Chang YT，Huang CW，et al. Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer′s disease [J]. Alzheimers Res Ther，2018，10（1）：17-28.
[9] Karlnoski R，Wilcock D，Dickey C，et al. Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection [J]. Neurobiol Dis，2007，25（1）：179-188.
[10] Samuel S，Beljanski V，Van Grevenynghe J，et al. Bcl-2 inhibitors sensitize therapy-resistant chronic lymphocytic leukemia cells to VSV oncolysis [J]. Mol Ther，2013，21（7）：1413-1423.
[11] Peter B，Cerny-Reiterer S，Hadzijusufovic E，et al. The pan-Bcl-2 blocker obatoclax promotes the expression of Puma，Noxa，and Bim mRNA and induces apoptosis in neoplastic mast cells [J]. J Leukoc Biol，2014，95（1）：95-104.
[12] Martini F，Rosa SG，Klann IP，et al. A multifunctional compound ebselen reverses memory impairment，apoptosis and oxidative stress in a mouse model of sporadic Alzheimer′s disease [J]. J Psychiatr Res，2019，109：107-117.
[13] Shi J， Zhang X，Ni J，et al. The influence of GAPT extraction on synapse loss of APPswe/PS1dE9 transgenic mice via adjusting Bcl-2 /Bax balance [J]. Alzheimers Dement，2018，4：724-736.
[14] Yeganeh B，Mehrpour M，Kashani HH，et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders [J]. Prog Neurobiol，2014，112：24-49.
[15] Martini F，Rosa SG，Klann IP，et al. A multifunctional compound ebselen reverses memory impairment，apoptosis and oxidative stress in a mouse model of sporadic Alzheimer′s disease [J]. J Psychiatr Res，2019，109：107-117.
[16] Rogers C，Fernandes-Alnemri T，Mayes L，et al. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death [J]. Nat Commun，2017，8：14 128-14 141.
[17] Xu P，Cai X，Zhang W，et al. Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2 （Ca（2+））/Caspase-3/PARP-1 pathway [J]. Apoptosis，2016，21（10）：1125-1143.
[18] Shirotani K，Tomioka M，Kremmer E，et al. Pathological activity of familial Alzheimer′s disease-associated mutant presenilin can be executed by six different gamma-secretasecomplexes [J]. Neurobiol Dis，2007，27（1）：102-107.
[19] Castro TG，Munteanu FD，Cavaco-Paulo A，et al. Electrostatics of Tau Protein by Molecular Dynamics [J]. Biomolecules，2019，9（3）：116-131.
[20] Rohn TT，Vyas V，Hernandez-Estrad T，et al. Lack of Pathology in a Triple Transgenic Mouse Model of Alzheimer′s Disease after Overexpression of the Anti-Apoptotic Protein Bcl-2 [J]. J Neurosci，2008，28（12）：3051-3059.
[21] Yeh PA，Chang CJ，Tu PH，et al. Phosphorylation alters Tau distribution and elongates life span in Drosophila [J]. J Alzheimers Dis，2010，21（2）：543-556.
2019, Vol. 16 
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