颞叶癫痫海马组织中相关蛋白及通道的研究进展_Journal of Epilepsy

Authors：

李柯麓 ,  任惠

昆明医科大学第一附属医院干疗神经内科（昆明 650032）;

Corresponding author：

任惠, Email: HuiRen2006@163.com

Keywords：

颞叶癫痫; 海马; 蛋白质组学

DOI：

10.7507/2096-0247.20180082

Video：

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癫痫发生在全球约 1%～2% 的人群中，其特点是周期性和不可预测的重复性癫痫发作并伴有急性全身和神经损伤。其中大多数药物难治性癫痫病例为颞叶癫痫（TLE），是一种类型相当独特的癫痫综合症，其发病机制尚不明确，可能与基因表达模式、细胞凋亡、神经胶质细胞增生、神经传递和信号传导异常，以及受体功能紊乱等有关。目前人类颞叶脑组织和癫痫动物模型发现了一系列的蛋白以及其涉及的相应信号通路参与 TLE 的形成，文章翻阅和整理了大量国内外相关文献，对 TLE 海马组织中相关蛋白及通道进行汇总，期望对临床治疗难治性癫痫提供依据和指导。

Citation： 李柯麓, 任惠. 颞叶癫痫海马组织中相关蛋白及通道的研究进展. Journal of Epilepsy, 2018, 4(6): 509-512. doi: 10.7507/2096-0247.20180082 Copy

1.	Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task force on classification and terminology. Epilepsia, 2001, 42(6): 796-803.
2.	Chang BS, Lowenstein DH. Epilepsy. N Engl J Med, 2003, 349(13): 1257-1266.
3.	Liu X, Wen F, Yang J, et al. A review of current applications of mass spectrometry for neuroproteomics in epilepsy. Mass Spectrom Rev, 2010, 29(2): 197-246.
4.	Lanneau D, Wettstein G, Bonniaud P, et al. Heat shock proteins: cell protection through protein triage. Scientific World Journal, 2010, 10: 1543-1552.
5.	Chang CC, Lui CC, Lee CC, et al. Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy. BMC Neurol, 2012, 12: 15.
6.	Kirschstein T, Mikkat S, Mikkat U, et al. The 27-kDa heat shock protein (HSP27) is a reliable hippocampal marker of full development of pilocarpine-induced status epilepticus. Epilepsy Res, 2012, 98(1): 35-43.
7.	Rogemond V, Auger C, Giraudon P, et al. Processing and nuclear localization of CRMP2 during brain development induce neurite outgrowth inhibition. J Biol Chem, 2008, 283(21): 14751-14561.
8.	Rogawski MA, Tofighy A, White HS, et al. Current understanding of the mechanism of action of the antiepileptic drug lacosamide. Epilepsy Res, 2015, 110: 189-205.
9.	Wilson SM, Moutal A, Melemedjian OK, et al. The functionalized amino acid (S)-Lacosamide subverts CRMP2-mediated tubulin polymerization to prevent constitutive and activity-dependent increase in neurite outgrowth. Front Cell Neurosci, 2014, 8: 196.
10.	Lee CY, Jaw T, Tseng HC, et al. Lovastatin modulates glycogen synthase kinase-3beta pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus. PLoS One, 2012, 7(6): e38789.
11.	Ohlsson M, Mattsson P, Wamil BD, et al. Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve. Restor Neurol Neurosci, 2004, 22(1): 33-41.
12.	Focking M, Chen WQ, Dicker P, et al. Proteomic analysis of human hippocampus shows differential protein expression in the different hippocampal subfields. Proteomics, 2012, 12(15-16): 2477-2481.
13.	Lee TS, Mane S, Eid T, et al. Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol Med, 2007, 13(1-2): 1-13.
14.	Duncan RL, Turner CH. Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int, 1995, 57(5): 344-358.
15.	Wu Y, Wang XF, Mo XA, et al. Expression of laminin beta1 and integrin alpha2 in the anterior temporal neocortex tissue of patients with intractable epilepsy. Int J Neurosci, 2011, 121(6): 323-328.
16.	Wu Y, Feng Y, Pang JR, et al. Study on expression of laminin in patients with intractable epilepsy. Int J Neurosci, 2009, 119(12): 2219-2227.
17.	Cheng J, Zhang J, Merched A, et al. Mechanical stretch inhibits oxidized low density lipoprotein-induced apoptosis in vascular smooth muscle cells by up-regulating integrin alphavbeta3 and stablization of PINCH-1. J Biol Chem, 2007, 282(47): 34268-34275.
18.	Liu GL, Wang KY, Guo H, et al. Inositol-requiring protein 1alpha signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy. Neurol Sci, 2013, 34(3): 357-364.
19.	Liang P, MacRae TH. Molecular chaperones and the cytoskeleton. J Cell Sci, 1997, 110(Pt 13): 1431-1440.
20.	Yamamoto A, Murphy N, Schindler CK, et al. Endoplasmic reticulum stress and apoptosis signaling in human temporal lobe epilepsy. J Neuropathol Exp Neurol, 2006, 65(3): 217-225.
21.	Yu Z, Luo H, Fu W, et al. The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol, 1999, 155(2): 302-314.
22.	Sato K, Abe K. Increases in mRNA levels for Talpha1-tubulin in the rat kindling model of epilepsy. Brain Res, 2001, 904(1): 157-160.
23.	Yang JW, Czech T, Felizardo M, et al. Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. Amino Acids, 2006, 30(4): 477-493.
24.	Hendriksen H, Datson NA, Ghijsen WE, et al. Altered hippocampal gene expression prior to the onset of spontaneous seizures in the rat post-status epilepticus model. Eur J Neurosci, 2001, 14(9): 1475-1484.
25.	Nemani VM, Binder DK. Emerging role of gap junctions in epilepsy. Histol Histopathol, 2005, 20(1): 253-259.
26.	Gajda Z, Gyengesi E, Hermesz E, et al. Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo. Epilepsia, 2003, 44(12): 1596-1600.
27.	李雪斌, 黄瑞雅, 吴晓飞, 等. 颞叶癫痫大鼠缝隙连接蛋白 32 表达变化的实验研究. 卒中与精神疾病, 2010, 20(5): 702-705.
28.	Zappala A, Li Volti G, Serapide MF, et al. Expression of pannexin2 protein in healthy and ischemized brain of adult rats. Neuroscience, 2007, 148(3): 653-667.
29.	Fedele DE, Gouder N, Guttinger M, et al. Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation. Brain, 2005, 128(Pt 10): 2383-2395.
30.	Sha L, Wu X, Yao Y, et al. Notch signaling activation promotes seizure activity in temporal lobe epilepsy. Mol Neurobiol, 2014, 49(2): 633-644.
31.	Vazquez G, Wedel BJ, Aziz O, et al. The mammalian TRPC cation channels. Biochim Biophys Acta, 2004, 1742(1-3): 21-36.
32.	Kunert-Keil C, Bisping F, Kruger J, et al. Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics, 2006, 7: 159.
33.	Zeng C, Zhou P, Jiang T, et al. Upregulation and diverse roles of TRPC3 and TRPC6 in synaptic reorganization of the mossy fiber pathway in temporal lobe epilepsy. Mol Neurobiol, 2015, 52(1): 562-572.
34.	Noreen M, Shah MA, Mall SM, et al. TLR4 polymorphisms and disease susceptibility. Inflamm Res, 2012, 61(3): 177-188.
35.	Derkow K, Kruger C, Dembny P, et al. Microglia induce neurotoxic IL-17⁺ gammadelta T cells dependent on TLR2, TLR4, and TLR9 activation. PLoS One, 2015, 10(8): e0135898.
36.	Cho KO, Lybrand ZR, Ito N, et al. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nat Commun, 2015, 6: 6606.

1. Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task force on classification and terminology. Epilepsia, 2001, 42(6): 796-803.
2. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med, 2003, 349(13): 1257-1266.
3. Liu X, Wen F, Yang J, et al. A review of current applications of mass spectrometry for neuroproteomics in epilepsy. Mass Spectrom Rev, 2010, 29(2): 197-246.
4. Lanneau D, Wettstein G, Bonniaud P, et al. Heat shock proteins: cell protection through protein triage. Scientific World Journal, 2010, 10: 1543-1552.
5. Chang CC, Lui CC, Lee CC, et al. Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy. BMC Neurol, 2012, 12: 15.
6. Kirschstein T, Mikkat S, Mikkat U, et al. The 27-kDa heat shock protein (HSP27) is a reliable hippocampal marker of full development of pilocarpine-induced status epilepticus. Epilepsy Res, 2012, 98(1): 35-43.
7. Rogemond V, Auger C, Giraudon P, et al. Processing and nuclear localization of CRMP2 during brain development induce neurite outgrowth inhibition. J Biol Chem, 2008, 283(21): 14751-14561.
8. Rogawski MA, Tofighy A, White HS, et al. Current understanding of the mechanism of action of the antiepileptic drug lacosamide. Epilepsy Res, 2015, 110: 189-205.
9. Wilson SM, Moutal A, Melemedjian OK, et al. The functionalized amino acid (S)-Lacosamide subverts CRMP2-mediated tubulin polymerization to prevent constitutive and activity-dependent increase in neurite outgrowth. Front Cell Neurosci, 2014, 8: 196.
10. Lee CY, Jaw T, Tseng HC, et al. Lovastatin modulates glycogen synthase kinase-3beta pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus. PLoS One, 2012, 7(6): e38789.
11. Ohlsson M, Mattsson P, Wamil BD, et al. Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve. Restor Neurol Neurosci, 2004, 22(1): 33-41.
12. Focking M, Chen WQ, Dicker P, et al. Proteomic analysis of human hippocampus shows differential protein expression in the different hippocampal subfields. Proteomics, 2012, 12(15-16): 2477-2481.
13. Lee TS, Mane S, Eid T, et al. Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol Med, 2007, 13(1-2): 1-13.
14. Duncan RL, Turner CH. Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int, 1995, 57(5): 344-358.
15. Wu Y, Wang XF, Mo XA, et al. Expression of laminin beta1 and integrin alpha2 in the anterior temporal neocortex tissue of patients with intractable epilepsy. Int J Neurosci, 2011, 121(6): 323-328.
16. Wu Y, Feng Y, Pang JR, et al. Study on expression of laminin in patients with intractable epilepsy. Int J Neurosci, 2009, 119(12): 2219-2227.
17. Cheng J, Zhang J, Merched A, et al. Mechanical stretch inhibits oxidized low density lipoprotein-induced apoptosis in vascular smooth muscle cells by up-regulating integrin alphavbeta3 and stablization of PINCH-1. J Biol Chem, 2007, 282(47): 34268-34275.
18. Liu GL, Wang KY, Guo H, et al. Inositol-requiring protein 1alpha signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy. Neurol Sci, 2013, 34(3): 357-364.
19. Liang P, MacRae TH. Molecular chaperones and the cytoskeleton. J Cell Sci, 1997, 110(Pt 13): 1431-1440.
20. Yamamoto A, Murphy N, Schindler CK, et al. Endoplasmic reticulum stress and apoptosis signaling in human temporal lobe epilepsy. J Neuropathol Exp Neurol, 2006, 65(3): 217-225.
21. Yu Z, Luo H, Fu W, et al. The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol, 1999, 155(2): 302-314.
22. Sato K, Abe K. Increases in mRNA levels for Talpha1-tubulin in the rat kindling model of epilepsy. Brain Res, 2001, 904(1): 157-160.
23. Yang JW, Czech T, Felizardo M, et al. Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. Amino Acids, 2006, 30(4): 477-493.
24. Hendriksen H, Datson NA, Ghijsen WE, et al. Altered hippocampal gene expression prior to the onset of spontaneous seizures in the rat post-status epilepticus model. Eur J Neurosci, 2001, 14(9): 1475-1484.
25. Nemani VM, Binder DK. Emerging role of gap junctions in epilepsy. Histol Histopathol, 2005, 20(1): 253-259.
26. Gajda Z, Gyengesi E, Hermesz E, et al. Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo. Epilepsia, 2003, 44(12): 1596-1600.
27. 李雪斌, 黄瑞雅, 吴晓飞, 等. 颞叶癫痫大鼠缝隙连接蛋白 32 表达变化的实验研究. 卒中与精神疾病, 2010, 20(5): 702-705.
28. Zappala A, Li Volti G, Serapide MF, et al. Expression of pannexin2 protein in healthy and ischemized brain of adult rats. Neuroscience, 2007, 148(3): 653-667.
29. Fedele DE, Gouder N, Guttinger M, et al. Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation. Brain, 2005, 128(Pt 10): 2383-2395.
30. Sha L, Wu X, Yao Y, et al. Notch signaling activation promotes seizure activity in temporal lobe epilepsy. Mol Neurobiol, 2014, 49(2): 633-644.
31. Vazquez G, Wedel BJ, Aziz O, et al. The mammalian TRPC cation channels. Biochim Biophys Acta, 2004, 1742(1-3): 21-36.
32. Kunert-Keil C, Bisping F, Kruger J, et al. Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics, 2006, 7: 159.
33. Zeng C, Zhou P, Jiang T, et al. Upregulation and diverse roles of TRPC3 and TRPC6 in synaptic reorganization of the mossy fiber pathway in temporal lobe epilepsy. Mol Neurobiol, 2015, 52(1): 562-572.
34. Noreen M, Shah MA, Mall SM, et al. TLR4 polymorphisms and disease susceptibility. Inflamm Res, 2012, 61(3): 177-188.
35. Derkow K, Kruger C, Dembny P, et al. Microglia induce neurotoxic IL-17⁺ gammadelta T cells dependent on TLR2, TLR4, and TLR9 activation. PLoS One, 2015, 10(8): e0135898.
36. Cho KO, Lybrand ZR, Ito N, et al. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nat Commun, 2015, 6: 6606.

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