四氢孕酮与阿兹海默症

张晖综述许百男审校

武警医学 ›› 2016, Vol. 27 ›› Issue (1) : 88-91.

PDF(632 KB)
PDF(632 KB)
武警医学 ›› 2016, Vol. 27 ›› Issue (1) : 88-91.
综述

四氢孕酮与阿兹海默症

  • 张晖1,2综述许百男1审校
作者信息 +
文章历史 +

摘要

阿兹海默症(Alzheimer’s disease, AD)是一种以认知功能障碍、记忆力衰退、人格异常等为主要特征的慢性中枢性神经系统退行性疾病。其特征性病理表现是神经纤维缠结、老年斑、神经元细胞丢失等[1]。流行病学显示,AD的发病率日益增高,成为目前威胁老年人健康的重要疾病。预计至2050年,患病人数将是目前的4倍[2]。本病病因尚不明确,可能包括多种因素,如氧化应激、线粒体功能障碍、炎性反应、能量代谢不平衡、神经甾体分泌不足等。笔者主要对四氢孕酮(allopregnanolone, APα)这一重要的神经甾体激素在AD中预防和治疗的作用及其可能机制做一综述。

关键词

四氢孕酮 / 阿兹海默症 / 神经甾体激素

引用本文

导出引用
张晖综述许百男审校. 四氢孕酮与阿兹海默症[J]. 武警医学. 2016, 27(1): 88-91
中图分类号: R964    R966   

参考文献

[1] Perl D P. Neuropathology of Alzheimer’s disease [J]. Mt Sinai J Med, 2010 , 77(1):32-42.
[2] Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers [J]. Biochem Pharmacol, 2014, 88(4):640-651.
[3] Melcangi R C, Panzica G C. Allopregnanolone: state of the art [J]. Prog Neurobiol, 2014, 113:1-5.
[4] Rupprecht R, Papadopoulos V, Rammes G, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders [J]. Nat Rev Drug Discov, 2010, 9(12):971-988.
[5] Schumacher M, Mattern C, Ghoumari A, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors [J]. Prog Neurobiol, 2014, 113:6-39.
[6] Hosie A M, Wilkins M E, da Silva H M, et al. Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites [J]. Nature, 2006, 444(7118):486-489.
[7] Pinna G, Uzunova V, Matsumoto K, et al. Brain allopregnanolone regulates the potency of the GABA(A) receptor agonist muscimol [J]. Neuropharmacology, 2000, 39(3):440-448.
[8] Guidotti A, Dong E, Matsumoto K, et al. The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders [J]. Brain Res Brain Res Rev, 2001, 37(1-3):110-115.
[9] Singh A, Kumar A. Possible GABAergic modulation in the protective effect of allopregnanolone on sleep deprivation-induced anxiety-like behavior and oxidative damage in mice [J]. Methods Find Exp Clin Pharmacol 2008,30(9):681-689.
[10] Naylor J C, Kilts J D, Hulette C M, et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects [J]. Biochim Biophys Acta, 2010,1801(8):951-959.
[11] Marx C E, Trost W T, Shampine L J, et al. The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease [J]. Biol Psychiatry, 2006, 60(12):1287-1294.
[12] Singh M, Su C. Progesterone and neuroprotection [J]. Horm Behav, 2013, 63(2): 284-290.
[13] Singh C, Liu L, Wang J M, et al. Allopregnanolone restores hippocampal-dependent learning and memory and neural progenitor survival in aging 3xTgAD and nonTg mice [J]. Neurobiol Aging, 2012, 33(8):1493-1506.
[14] Wang J M, Singh C, Liu L, et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer’s disease [J]. Proc Natl Acad Sci U S A, 2010, 107(14): 6498-6503.
[15] Ardeshiri A, Kelley M H, Korner I P, et al. Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen-glucose deprivation [J]. Eur J Neurosci, 2006, 24(9):2567-2574.
[16] Irwin R W, Brinton R D. Allopregnanolone as regenerative therapeutic for Alzheimer's disease: translational development and clinical promise [J]. Prog Neurobiol, 2014, 113:40-55.
[17] Irwin R W, Solinsky C M, Loya C M, et al. Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer’s disease [J]. PLoS One, 2015, 10(6):e0128313.
[18] Timby E, Balgrd M, Nyberg S, et al. Pharmacokinetic and behavioral effects of allopregnanolone in healthy women[J]. Psychopharmacology (Berl), 2006, 186(3):414-424.
[19] Wang J M, Singh C, Liu L, et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer’s disease [J]. Proc Natl Acad Sci U S A, 2010, 107(14):6498-6503.
[20] de Quervain D J, Poirier R, Wollmer M A, et al. Glucocorticoid-related genetic susceptibility for Alzheimer's disease [J]. Hum Mol Genet, 2004, 13(1):47-52.
[21] Bengtsson S K, Johansson M, Bckstrm T, et al. Chronic allopregnanolone treatment accelerates Alzheimer's disease development in AβPP(Swe)PSEN1(ΔE9) mice [J]. J Alzheimers Dis, 2012, 31(1):71-84.
[22] Rabinowitz A, Cohen SJ, Finn D A, et al. The neurosteroid allopregnanolone impairs object memory and contextual fear memory in male C57BL/6J mice [J]. Horm Behav, 2014, 66(2):238-246.
[23] Yawno T, Hirst J J, Castillo-Melendez M, et al. Role of neurosteroids in regulating cell death and proliferation in the late gestation fetal brain [J]. Neuroscience,2009, 163(3):838-847.
[24] Brinton R D. Neurosteroids as regenerative agents in the brain: therapeutic implications [J]. Nat Rev Endocrinol, 2013, 9(4):241-250.
[25] Wang J M, Johnston P B, Ball B G, et al. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression [J]. J Neurosci, 2005, 25(19):4706-4718.
[26] Sun C, Ou X, Farley J M, et al. Allopregnanolone increases the number of dopaminergic neurons in substantia nigra of a triple transgenic mouse model of Alzheimer’s disease [J]. Curr Alzheimer Res, 2012, 9(4):473-480.
[27] Guennoun R, Labombarda F, Gonzalez Deniselle M C, et al. Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection [J]. J Steroid Biochem Mol Biol, 2015, 146:48-61.
[28] Miri A, Daie K, Burdine R D, et al. Regression-based identification of behavior-encoding neurons during large-scale optical imaging of neural activity at cellular resolution [J]. J Neurophysiol, 2011, 105(2):964-980.
[29] Brinton R D, Wang J M. Preclinical analyses of the therapeutic potential of allopregnanolone to promote neurogenesis in vitro and in vivo in transgenic mouse model of Alzheimer’s disease [J].Curr Alzheimer Res, 2006, 3(1): 11-17.
[30] Wang J M, Brinton R D. Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential [J]. BMC Neurosci, 2008, 9 (Suppl 2):S11.
[31] Leskiewicz M, Regulska M, Budziszewska B, et al. Effects of neurosteroids on hydrogen peroxide- and staurosporine-induced damage of human neuroblastoma SH-SY5Y cells [J]. J Neurosci Res, 2008, 86(6):1361-1370.
[32] Lockhart E M, Warner D S, Pearlstein R D, et al. Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture [J]. Neurosci Lett, 2002, 328(1):33-36.
[33] 李贤慧,张新昌,王 刚, 等. 神经活性甾体别孕烯醇酮对脑皮质神经元损伤的保护作用 [J]. 中国应用生理学杂志, 2011, 27(2):175-178.
[34] Xilouri M, Papazafiri P. Anti-apoptotic effects of allopregnanolone on P19 neurons [J]. Eur J Neurosci, 2006, 23(1):43-54.
[35] Gartside S E,Griffith N C,Kaura V,et al.The neurosteroid dehydroepiandrosterone ( DHEA) and its metabolites alter 5-HT neuronal activity via modulation of GABAA receptors [J].J Psychopharmacol, 2010, 24(11): 1717-1724.
[36] Charalampopoulos I, Alexaki VI, Tsatsanis C, et al. Neurosteroids as endogenous inhibitors of neuronal cell apoptosis in aging [J]. Ann N Y Acad Sci, 2006, 1088:139-152.
[37] Sayeed I, Parvez S, Wali B, et al. Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism for better neuroprotective effects of allopregnanolone over progesterone [J]. Brain Res, 2009, 1263:165-173.

PDF(632 KB)

Accesses

Citation

Detail

段落导航
相关文章

/