Login Register Cart 0
Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Review Article

易位蛋白在阿尔茨海默氏病脑中的保护作用

卷 17, 期 1, 2020

页: [3 - 15] 页: 13

弟呕挨: 10.2174/1567205017666200217105950

价格: $65

摘要

转运蛋白（18 kDa）（TSPO）是一种线粒体蛋白，可将胞质胆固醇定位于线粒体膜上，从而开始合成包括神经营养性神经甾体在内的甾体。 TSPO大量存在于支持神经元并对神经炎症作出反应的神经胶质细胞中。 TSPO位于线粒体的外膜，调节线粒体通透性过渡孔（mPTP）的开口，该孔控制线粒体功能所需的分子的进入。 TSPO与神经退行性阿尔茨海默氏病（AD）相关，因此TSPO在AD患者的大脑中被上调并发出AD引起的大脑不良变化的信号。响应于脑损伤的TSPO的最初增加仍然升高，以修复细胞损伤，并可能随着AD的进行而防止进一步的神经元变性。为了发挥这种保护作用，TSPO增加了神经保护性类固醇的合成，减少了神经炎症，限制了mPTP的开放，并减少了活性氧的产生。 TSPO对AD脑的有益作用表现为神经毒性淀粉样β的减轻和线粒体功能障碍，并伴有记忆力和认知能力的改善。但是，随着AD严重程度的提高，TSPO的保护活性似乎是暂时的，并最终减弱。在失去内源性TSPO活性之前，及时用TSPO激动剂/配体治疗可能会增强保护功能，并可能延长神经元的存活时间。

关键词: 阿尔茨海默氏病（AD），β淀粉样蛋白，神经类固醇，线粒体通透性过渡孔，活性氧，转运蛋白（18 kDa）。

« Previous Next »
[1]
Papadopoulos V, Baraldi M, Guilarte TR, Thomas B Knudsen, Jean-Jacques Lacapère, et al. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 27(8): 402-9. (2006).
[http://dx.doi.org/10.1016/j.tips.2006.06.005] [PMID: 16822554 ]
[2]
Basile AS, Skolnick P. Subcellular localization of “peripheral-type” binding sites for benzodiazepines in rat brain. J Neurochem 46(1): 305-8. (1986).
[http://dx.doi.org/10.1111/j.1471-4159.1986.tb12965.x] [PMID: 2999338]
[3]
Braestrup C, Squires RF. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proc Natl Acad Sci USA 74(9): 3805-9. (1977).
[http://dx.doi.org/10.1073/pnas.74.9.3805] [PMID: 20632]
[4]
Iversen P, Hansen DA, Bender D, Rodell A, Munk OL, Cumming P, et al. Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy. Eur J Nucl Med Mol Imaging 33(7): 810-6. (2006).
[http://dx.doi.org/10.1007/s00259-005-0052-8] [PMID: 16550382]
[5]
Papadopoulos V, Amri H, Boujrad N, Culty M, Garnier M, Hardwick M, et al. Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis. Steroids 62(1): 21-8. (1997).
[http://dx.doi.org/10.1016/S0039-128X(96)00154-7] [PMID: 9029710]
[6]
Rone MB, Liu J, Blonder J, Ye X, Veenstra TD, Young JC, et al. Targeting and insertion of the cholesterol-binding translocator protein into the outer mitochondrial membrane. Biochemistry 48(29): 6909-20. (2009).
[http://dx.doi.org/10.1021/bi900854z] [PMID: 19552401]
[7]
Barron AM, Ji B, Kito S, Suhara T, Higuchi M. Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male. Biochem J 475(1): 75-85. (2018).
[http://dx.doi.org/10.1042/BCJ20170645] [PMID: 29127254]
[8]
Hamelin L, Lagarde J, Dorothée G, Potier MC, Corlier F, Kuhnast B, et al. Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer’s disease. Brain 141(6): 1855-70. (2018).
[http://dx.doi.org/10.1093/brain/awy079] [PMID: 29608645]
[9]
Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, et al. In-vivo measurement of activated microglia in dementia. Lancet 358(9280): 461-7. (2001).
[http://dx.doi.org/10.1016/S0140-6736(01)05625-2] [PMID: 11513911]
[10]
Gulyás B, Vas A, Tóth M, Takano A, Varrone A, Cselényi Z, et al. Age and disease related changes in the translocator protein (TSPO) system in the human brain: positron emission tomography measurements with [11C]vinpocetine. Neuroimage 56(3): 1111-21. (2011).
[http://dx.doi.org/10.1016/j.neuroimage.2011.02.020] [PMID: 21320609]
[11]
Gulyás B, Makkai B, Kása P, Gulya K, Bakota L, Várszegi S, et al. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system. Neurochem Int 54(1): 28-36. (2009).
[http://dx.doi.org/10.1016/j.neuint.2008.10.001] [PMID: 18984021]
[12]
Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: An [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis 32(3): 412-9. (2008).
[http://dx.doi.org/10.1016/j.nbd.2008.08.001] [PMID: 18786637]
[13]
Yasuno F, Ota M, Kosaka J, Ito H, Higuchi M, Doronbekov TK, et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry 64(10): 835-41. (2008).
[http://dx.doi.org/10.1016/j.biopsych.2008.04.021] [PMID: 18514164]
[14]
Kircher T, Wormstall H. Alois Alzheimer (1864-1915)--student days and first scientific activities. J Geriatr Psychiatry Neurol 10(3): 127-9. (1997).
[http://dx.doi.org/10.1177/089198879701000307] [PMID: 9322136]
[15]
Tandon A, Fraser P. The presenilins. Genome Biol 3: 30141-9. (2002).
[16]
Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 68(7): 501-8. (2007).
[http://dx.doi.org/10.1212/01.wnl.0000244749.20056.d4] [PMID: 17065593]
[17]
Kreisl WC, Lyoo CH, Liow JS, Monica Wei, Joseph Snow, Emily Page, et al. (11)C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease. Neurobiol Aging 44: 53-61. (2016).
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.011] [PMID: 27318133]
[18]
Fan Z, Dani M, Femminella GD, Wood M, Calsolaro V, Veronese M, et al. Parametric mapping using spectral analysis for 11C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects. Eur J Nucl Med Mol Imaging 45(8): 1432-41. (2018).
[http://dx.doi.org/10.1007/s00259-018-3984-5] [PMID: 29523926]
[19]
Au E, Richter MW, Vincent AJ, Tetzlaff W, Aebersold R, Sage EH, et al. SPARC from olfactory ensheathing cells stimulates Schwann cells to promote neurite outgrowth and enhances spinal cord repair. J Neurosci 27(27): 7208-21. (2007).
[http://dx.doi.org/10.1523/JNEUROSCI.0509-07.2007] [PMID: 17611274]
[20]
Choi J, Ifuku M, Noda M, Guilarte TR. Translocator protein (18 kDa)/peripheral benzodiazepine receptor specific ligands induce microglia functions consistent with an activated state. Glia 59(2): 219-30. (2011).
[http://dx.doi.org/10.1002/glia.21091] [PMID: 21125642]
[21]
Nakajima K, Kanamatsu T, Koshimoto M, Kohsaka S. Microglia derived from the axotomized adult rat facial nucleus uptake glutamate and metabolize it to glutamine in vitro. Neurochem Int 102: 1-12. (2017).
[http://dx.doi.org/10.1016/j.neuint.2016.10.015] [PMID: 27816478]
[22]
Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, et al. Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci 16(5): 543-51. (2013).
[http://dx.doi.org/10.1038/nn.3358] [PMID: 23525041]
[23]
Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong J-S, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55(5): 453-62. (2007).
[http://dx.doi.org/10.1002/glia.20467] [PMID: 17203472]
[24]
Hanisch UK. Microglia as a source and target of cytokines. Glia 40(2): 140-55. (2002).
[http://dx.doi.org/10.1002/glia.10161] [PMID: 12379902]
[25]
Borst K, Schwabenland M, Prinz M. Microglia metabolism in health and disease. Neurochem Int 130 104331 (2019).
[http://dx.doi.org/10.1016/j.neuint.2018.11.006] [PMID: 30423423]
[26]
McGeer PL, Itagaki S, Tago H, McGeer EG. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79(1-2): 195-200. (1987).
[http://dx.doi.org/10.1016/0304-3940(87)90696-3] [PMID: 3670729]
[27]
Nagai A, Nakagawa E, Hatori K, Choi HB, McLarnon JG, Lee MA, et al. Generation and characterization of immortalized human microglial cell lines: expression of cytokines and chemokines. Neurobiol Dis 8(6): 1057-68. (2001).
[http://dx.doi.org/10.1006/nbdi.2001.0437] [PMID: 11741401]
[28]
Benavides J, Dubois A, Scatton B. Peripheral type benzodiazepine binding sites as a tool for the detection and quantification of CNS injury. In: Curr Protoc Neurosci. 2001. Chapter 7: p. Unit7 16.
[29]
Zhao YY, Yu JZ, Li QY, Ma CG, Lu CZ, Xiao BG. TSPO-specific ligand vinpocetine exerts a neuroprotective effect by suppressing microglial inflammation. Neuron Glia Biol 7(2-4): 187-97. (2011).
[http://dx.doi.org/10.1017/S1740925X12000129] [PMID: 22874716]
[30]
Zhou X, Dong XW, Crona J, Maguire M, Priestley T. Vinpocetine is a potent blocker of rat NaV1.8 tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 306(2): 498-504. (2003).
[http://dx.doi.org/10.1124/jpet.103.051086] [PMID: 12730276]
[31]
Ahn HS, Crim W, Romano M, Sybertz E, Pitts B. Effects of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta. Biochem Pharmacol 38(19): 3331-9. (1989).
[http://dx.doi.org/10.1016/0006-2952(89)90631-X] [PMID: 2554921]
[32]
Jeon KI, Xu X, Aizawa T, Lim JH, Jono H, Kwon D-S, et al. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci USA 107(21): 9795-800. (2010).
[http://dx.doi.org/10.1073/pnas.0914414107] [PMID: 20448200]
[33]
López-Picón FR, Snellman A, Eskola O, Helin S, Solin O, Haaparanta-Solin M, et al. Neuroinflammation appears early on PET Imaging and then plateaus in a mouse model of Alzheimer disease. J Nucl Med 59(3): 509-15. (2018).
[http://dx.doi.org/10.2967/jnumed.117.197608] [PMID: 28986511]
[34]
Frost GR, Li YM. The role of astrocytes in amyloid production and Alzheimer’s disease. Open Biol 7(12): 7. (2017).
[http://dx.doi.org/10.1098/rsob.170228] [PMID: 29237809]
[35]
Giatti S, Pesaresi M, Cavaletti G, R Bianchi, V Carozzi, R Lombardi, et al. Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro5-4864) in experimental diabetic neuropathy. Neuroscience 164(2): 520-9. (2009).
[http://dx.doi.org/10.1016/j.neuroscience.2009.08.005] [PMID: 19665520]
[36]
Agnello D, Carvelli L, Muzio V, Villa P, Bottazzi B, Polentarutti N, et al. Increased peripheral benzodiazepine binding sites and pentraxin 3 expression in the spinal cord during EAE: relation to inflammatory cytokines and modulation by dexamethasone and rolipram. J Neuroimmunol 109(2): 105-11. (2000).
[http://dx.doi.org/10.1016/S0165-5728(00)00279-4] [PMID: 10996212]
[37]
Chen MK, Baidoo K, Verina T, Guilarte TR. Peripheral benzodiazepine receptor imaging in CNS demyelination: functional implications of anatomical and cellular localization. Brain 127(Pt 6): 1379-92. (2004).
[http://dx.doi.org/10.1093/brain/awh161] [PMID: 15069023]
[38]
Chen MK, Guilarte TR. Imaging the peripheral benzodiazepine receptor response in central nervous system demyelination and remyelination. Toxicol Sci 91(2): 532-9. (2006).
[http://dx.doi.org/10.1093/toxsci/kfj172] [PMID: 16554315]
[39]
Ji B, Maeda J, Sawada M, Ono M, Okauchi T, Inaji M, et al. Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer’s and other CNS pathologies. J Neurosci 28(47): 12255-67. (2008).
[http://dx.doi.org/10.1523/JNEUROSCI.2312-08.2008] [PMID: 19020019]
[40]
Veiga S, Azcoitia I, Garcia-Segura LM. Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity. J Neurosci Res 80(1): 129-37. (2005).
[http://dx.doi.org/10.1002/jnr.20430] [PMID: 15696538]
[41]
Soustiel JF, Zaaroor M, Vlodavsky E, Veenman L, Weizman A, Gavish M. Neuroprotective effect of Ro5-4864 following brain injury. Exp Neurol 214(2): 201-8. (2008).
[http://dx.doi.org/10.1016/j.expneurol.2008.08.008] [PMID: 18789929]
[42]
Gong J, Szego EM, Leonov A, Benito E, Becker S, Fischer A, et al. Translocator protein ligand protects against neurodegeneration in the MPTP mouse model of Parkinsonism. J Neurosci 39(19): 3752-69. (2019).
[http://dx.doi.org/10.1523/JNEUROSCI.2070-18.2019] [PMID: 30796158]
[43]
Bordet T, Buisson B, Michaud M, Drouot C, Galéa P, Delaage P, et al. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther 322(2): 709-20. (2007).
[http://dx.doi.org/10.1124/jpet.107.123000] [PMID: 17496168]
[44]
Ferzaz B, Brault E, Bourliaud G, Robert J-P, Poughon G, Claustre Y, et al. SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a peripheral benzodiazepine receptor ligand, promotes neuronal survival and repair. J Pharmacol Exp Ther 301(3): 1067-78. (2002).
[http://dx.doi.org/10.1124/jpet.301.3.1067] [PMID: 12023539]
[45]
Le Fur G, Vaucher N, Perrier ML, Flamier A, Benavides J, Renault C, et al. Differentiation between two ligands for peripheral benzodiazepine binding sites, [3H]RO5-4864 and [3H]PK 11195, by thermodynamic studies. Life Sci 33(5): 449-57. (1983).
[http://dx.doi.org/10.1016/0024-3205(83)90794-4] [PMID: 6308375]
[46]
Schlichter R, Rybalchenko V, Poisbeau P, Verleye M, Gillardin J. Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine. Neuropharmacology 39(9): 1523-35. (2000).
[http://dx.doi.org/10.1016/S0028-3908(99)00253-1] [PMID: 10854897]
[47]
Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov 9(12): 971-88. (2010).
[http://dx.doi.org/10.1038/nrd3295] [PMID: 21119734]
[48]
Girard C, Liu S, Cadepond F, Adams D, Lacroix C, Verleye M, et al. Etifoxine improves peripheral nerve regeneration and functional recovery. Proc Natl Acad Sci USA 105(51): 20505-10. (2008).
[http://dx.doi.org/10.1073/pnas.0811201106] [PMID: 19075249]
[49]
Servant D, Graziani PL, Moyse D, Parquet PJ. Treatment of adjustment disorder with anxiety: efficacy and tolerance of etifoxine in a double-blind controlled study. Encephale 24(6): 569-74. (1998).
[PMID: 9949940]
[50]
Hamon A, Morel A, Hue B, Verleye M, Gillardin JM. The modulatory effects of the anxiolytic etifoxine on GABA(A) receptors are mediated by the beta subunit. Neuropharmacology 45(3): 293-303. (2003).
[http://dx.doi.org/10.1016/S0028-3908(03)00187-4] [PMID: 12871647]
[51]
Focke C, Blume T, Zott B, Shi Y, Deussing M, Peters F, et al. Early and longitudinal microglial activation but not amyloid accumulation predicts cognitive outcome in PS2APP mice. J Nucl Med 60(4): 548-54. (2019).
[http://dx.doi.org/10.2967/jnumed.118.217703] [PMID: 30262517]
[52]
Blume T, Focke C, Peters F, Deussing M, Albert NL, Lindner S, et al. Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo μPET-study. J Neuroinflammation 15(1): 307. (2018).
[http://dx.doi.org/10.1186/s12974-018-1347-6] [PMID: 30400912]
[53]
Wolf L, Bauer A, Melchner D, Hallof-Buestrich H, Stoertebecker P, Haen E, et al. Enhancing neurosteroid synthesis--relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines. Pharmacopsychiatry 48(2): 72-7. (2015).
[http://dx.doi.org/10.1055/s-0034-1398507] [PMID: 25654303]
[54]
Evans J, Sun Y, McGregor A, Connor B. Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress. Neuropharmacology 63(8): 1315-26. (2012).
[http://dx.doi.org/10.1016/j.neuropharm.2012.08.012] [PMID: 22939998]
[55]
Barron AM, Garcia-Segura LM, Caruso D, et al. Ligand for translocator protein reverses pathology in a mouse model of Alzheimer’s disease. J Neurosci 33(20): 8891-7. (2013).
[http://dx.doi.org/10.1523/JNEUROSCI.1350-13.2013] [PMID: 23678130]
[56]
Liu B, Le KX, Park MA, Wang S, Belanger AP, Dubey S, et al. In vivo detection of age- and disease-related increases in neuroinflammation by 18F-GE180 TSPO microPET imaging in wild-type and Alzheimer’s transgenic mice. J Neurosci 35: 15716-30. (2015).
[PMID: 26609163]
[57]
Rodrigue KM, Kennedy KM, Park DC. Beta-amyloid deposition and the aging brain. Neuropsychol Rev 19(4): 436-50. (2009).
[http://dx.doi.org/10.1007/s11065-009-9118-x] [PMID: 19908146]
[58]
Lin R, Angelin A, Da Settimo F, Martini C, Taliani S, Zhu S, et al. Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Ab42-induced neurodegeneration. Aging Cell 13(3): 507-18. (2014).
[http://dx.doi.org/10.1111/acel.12200] [PMID: 24977274]
[59]
Baulieu EE, Robel P, Schumacher M. Neurosteroids: beginning of the story. Int Rev Neurobiol 46: 1-32. (2001).
[http://dx.doi.org/10.1016/S0074-7742(01)46057-0] [PMID: 11599297]
[60]
Borowicz KK, Piskorska B, Banach M, Czuczwar SJ. Neuroprotective actions of neurosteroids. Front Endocrinol (Lausanne) 2: 50. (2011).
[http://dx.doi.org/10.3389/fendo.2011.00050] [PMID: 22649375]
[61]
Gursoy E, Cardounel A, Kalimi M. Pregnenolone protects mouse hippocampal (HT-22) cells against glutamate and amyloid beta protein toxicity. Neurochem Res 26(1): 15-21. (2001).
[http://dx.doi.org/10.1023/A:1007668213330] [PMID: 11358277]
[62]
Djebaili M, Hoffman SW, Stein DG. Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex. Neuroscience 123(2): 349-59. (2004).
[http://dx.doi.org/10.1016/j.neuroscience.2003.09.023] [PMID: 14698743]
[63]
Liao G, Cheung S, Galeano J, Ji AX, Qin Q, Bi X. Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1-/- mouse brain. Brain Res 1270: 140-51. (2009).
[http://dx.doi.org/10.1016/j.brainres.2009.03.027] [PMID: 19328188]
[64]
Ratner MH, Kumaresan V, Farb DH. Neurosteroid actions in memory and neurologic/neuropsychiatric disorders. Front Endocrinol (Lausanne) 10: 169. (2019).
[http://dx.doi.org/10.3389/fendo.2019.00169] [PMID: 31024441]
[65]
Daugherty DJ, Selvaraj V, Chechneva OV, Liu XB, Pleasure DE, Deng W. A TSPO ligand is protective in a mouse model of multiple sclerosis. EMBO Mol Med 5(6): 891-903. (2013).
[http://dx.doi.org/10.1002/emmm.201202124] [PMID: 23681668]
[66]
Papadopoulos V, Aghazadeh Y, Fan J, Campioli E, Zirkin B, Midzak A. Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis. Mol Cell Endocrinol 408: 90-8. (2015).
[http://dx.doi.org/10.1016/j.mce.2015.03.014] [PMID: 25818881]
[67]
Jordà EG, Jiménez A, Verdaguer E, Canudas AM, Folch J, Sureda FX, et al. Evidence in favour of a role for peripheral-type benzodiazepine receptor ligands in amplification of neuronal apoptosis. Apoptosis 10(1): 91-104. (2005).
[http://dx.doi.org/10.1007/s10495-005-6064-9] [PMID: 15711925]
[68]
Weill-Engerer S, David JP, Sazdovitch V, Liere P, Eychenne B, Pianos A, et al. Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients. J Clin Endocrinol Metab 87(11): 5138-43. (2002).
[http://dx.doi.org/10.1210/jc.2002-020878] [PMID: 12414884]
[69]
Ishunina TA, van Beurden D, van der Meulen G, Unmehopa UA, Hol EM, Huitinga I, et al. Diminished aromatase immunoreactivity in the hypothalamus, but not in the basal forebrain nuclei in Alzheimer’s disease. Neurobiol Aging 26(2): 173-94. (2005).
[http://dx.doi.org/10.1016/j.neurobiolaging.2004.03.010] [PMID: 15582747]
[70]
MacKenzie SM, Dewar D, Stewart W, Fraser R, Connell JM, Davies E. The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer’s tissue. J Endocrinol 196(1): 123-30. (2008).
[http://dx.doi.org/10.1677/JOE-07-0427] [PMID: 18180323]
[71]
Marx CE, Stevens RD, Shampine LJ, Uzunova V, Trost WT, Butterfield MI, et al. Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics. Neuropsychopharmacology 31(6): 1249-63. (2006).
[http://dx.doi.org/10.1038/sj.npp.1300952] [PMID: 16319920]
[72]
Luchetti S, Bossers K, Van de Bilt S, Agrapart V, Morales RR, Frajese GV, et al. Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer’s disease. Neurobiol Aging 32(11): 1964-76. (2011).
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.12.014] [PMID: 20045216]
[73]
Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer’s disease. J Neurosci 26(51): 13384-9. (2006).
[http://dx.doi.org/10.1523/JNEUROSCI.2514-06.2006] [PMID: 17182789]
[74]
Naylor JC, Kilts JD, Hulette CM, Steffens DC, Blazer DG, Ervin JF, et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer’s disease compared to cognitively intact control subjects. Biochim Biophys Acta 1801(8): 951-9. (2010).
[http://dx.doi.org/10.1016/j.bbalip.2010.05.006] [PMID: 20488256]
[75]
Marx CE, Trost WT, Shampine LJ, Stevens RD, Hulette CM, Steffens DC, et al. The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer’s disease. Biol Psychiatry 60(12): 1287-94. (2006).
[http://dx.doi.org/10.1016/j.biopsych.2006.06.017] [PMID: 16997284]
[76]
Caruso D, Barron AM, Brown MA, Abbiati F, Carrero P, Pike CJ, et al. Age-related changes in neuroactive steroid levels in 3xTg-AD mice. Neurobiol Aging 34(4): 1080-9. (2013).
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.10.007] [PMID: 23122920]
[77]
Chen S, Wang JM, Irwin RW, Yao J, Liu L, Brinton RD. Allopregnanolone promotes regeneration and reduces β-amyloid burden in a preclinical model of Alzheimer’s disease. PLoS One 6(8) e24293 (2011).
[http://dx.doi.org/10.1371/journal.pone.0024293] [PMID: 21918687]
[78]
Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 107(14): 6498-503. (2010).
[http://dx.doi.org/10.1073/pnas.1001422107] [PMID: 20231471]
[79]
Carroll JC, Rosario ER, Villamagna A, Pike CJ. Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTransgenic-Alzheimer’s disease mice. Endocrinology 151(6): 2713-22. (2010).
[http://dx.doi.org/10.1210/en.2009-1487] [PMID: 20410196]
[80]
Yue X, Lu M, Lancaster T, Cao P, Honda S-I, Staufenbiel M, et al. Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer’s disease animal model. Proc Natl Acad Sci USA 102(52): 19198-203. (2005).
[http://dx.doi.org/10.1073/pnas.0505203102] [PMID: 16365303]
[81]
Rupprecht R, Rammes G, Eser D, Baghai TC, Schüle C, Nothdurfter C, et al. Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects. Science 325(5939): 490-3. (2009).
[http://dx.doi.org/10.1126/science.1175055] [PMID: 19541954]
[82]
Nothdurfter C, Rammes G, Baghai TC, Schule C, Schumacher M, Papadopoulos V, et al. Translocator protein (18 kDa) as a target for novel anxiolytics with a favourable side-effect profile. J Neuroendocrinol 24: 82-92. (2012).
[83]
Kita A, Kinoshita T, Kohayakawa H, Furukawa K, Akaike A. Lack of tolerance to anxiolysis and withdrawal symptoms in mice repeatedly treated with AC-5216, a selective TSPO ligand. Prog Neuropsychopharmacol Biol Psychiatry 33(6): 1040-5. (2009).
[http://dx.doi.org/10.1016/j.pnpbp.2009.05.018] [PMID: 19497344]
[84]
D’Onofrio G, Panza F, Seripa D, Sancarlo D, Paris F, Cascavilla L, et al. The APOE polymorphism in Alzheimer’s disease patients with neuropsychiatric symptoms and syndromes. Int J Geriatr Psychiatry 26(10): 1062-70. (2011).
[http://dx.doi.org/10.1002/gps.2644] [PMID: 21905100]
[85]
Ismail Z, Gatchel J, Bateman DR, Barcelos-Ferreira R, Cantillon M, Jaeger J, et al. Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria. Int Psychogeriatr 30(2): 185-96. (2018).
[http://dx.doi.org/10.1017/S1041610217001880] [PMID: 28899446]
[86]
Halestrap AP, Brenner C. The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem 2003; 10(16): 1507-25.
[http://dx.doi.org/10.2174/0929867033457278] [PMID: 12871123]
[87]
Ludwig O, De Pinto V, Palmieri F, Benz R. Pore formation by the mitochondrial porin of rat brain in lipid bilayer membranes. Biochim Biophys Acta 860(2): 268-76. (1986).
[http://dx.doi.org/10.1016/0005-2736(86)90523-7] [PMID: 2427116]
[88]
Galluzzi L, Blomgren K, Kroemer G. Mitochondrial membrane permeabilization in neuronal injury. Nat Rev Neurosci 10(7): 481-94. (2009).
[http://dx.doi.org/10.1038/nrn2665] [PMID: 19543220]
[89]
Gatliff J, Campanella M. TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria. Biochem J 473(2): 107-21. (2016).
[http://dx.doi.org/10.1042/BJ20150899] [PMID: 26733718]
[90]
Parker MA, Bazan HE, Marcheselli V, Rodriguez de Turco EB, Bazan NG. Platelet-activating factor induces permeability transition and cytochrome c release in isolated brain mitochondria. J Neurosci Res 69(1): 39-50. (2002).
[http://dx.doi.org/10.1002/jnr.10235] [PMID: 12111814]
[91]
Obame FN, Zini R, Souktani R, Berdeaux A, Morin D. Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization. J Pharmacol Exp Ther 323(1): 336-45. (2007).
[http://dx.doi.org/10.1124/jpet.107.124255] [PMID: 17640950]
[92]
Wu Y, Shamoto-Nagai M, Maruyama W, Osawa T, Naoi M. Phytochemicals prevent mitochondrial membrane permeabilization and protect SH-SY5Y cells against apoptosis induced by PK11195, a ligand for outer membrane translocator protein. J Neural Transm (Vienna) 124(1): 89-98. (2017).
[http://dx.doi.org/10.1007/s00702-016-1624-4] [PMID: 27640013]
[93]
Naoi M, Maruyama W, Yi H. Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria. J Neural Transm (Vienna) 120(11): 1539-51. (2013).
[http://dx.doi.org/10.1007/s00702-013-1033-x] [PMID: 23681678]
[94]
Banati RB, Middleton RJ, Chan R, Hatty CR, Kam WW, Quin C, et al. Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nat Commun 5: 5452. (2014).
[http://dx.doi.org/10.1038/ncomms6452] [PMID: 25406832]
[95]
Azarashvili T, Grachev D, Krestinina O, Youri Evtodienko, Igor Yurkov, Vassilios Papadopoulos, et al. The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Cell Calcium 42(1): 27-39. (2007).
[http://dx.doi.org/10.1016/j.ceca.2006.11.004] [PMID: 17174393]
[96]
Kinnally KW, Zorov DB, Antonenko YN, Snyder SH, McEnery MW, Tedeschi H. Mitochondrial benzodiazepine receptor linked to inner membrane ion channels by nanomolar actions of ligands. Proc Natl Acad Sci USA 90(4): 1374-8. (1993).
[http://dx.doi.org/10.1073/pnas.90.4.1374] [PMID: 7679505]
[97]
Onyango IG, Dennis J, Khan SM. Mitochondrial dysfunction in Alzheimer’s disease and the rationale for bioenergetics based therapies. Aging Dis 7(2): 201-14. (2016).
[http://dx.doi.org/10.14336/AD.2015.1007] [PMID: 27114851]
[98]
Blass JP, Gibson GE. The role of oxidative abnormalities in the pathophysiology of Alzheimer’s disease. Rev Neurol (Paris) 147(6-7): 513-25. (1991).
[PMID: 1962057]
[99]
Gabuzda D, Busciglio J, Chen LB, Matsudaira P, Yankner BA. Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative. J Biol Chem 269(18): 13623-8. (1994).
[PMID: 8175797]
[100]
Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov P, Alafuzoff I, et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci USA 105(35): 13145-50. (2008).
[http://dx.doi.org/10.1073/pnas.0806192105] [PMID: 18757748]
[101]
Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JC, et al. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J 19(14): 2040-1. (2005).
[http://dx.doi.org/10.1096/fj.05-3735fje] [PMID: 16210396]
[102]
Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med 14(10): 1097-105. (2008).
[http://dx.doi.org/10.1038/nm.1868] [PMID: 18806802]
[103]
Zhang C, Rissman RA, Feng J. Characterization of ATP alternations in an Alzheimer’s disease transgenic mouse model. J Alzheimers Dis 44(2): 375-8. (2015).
[http://dx.doi.org/10.3233/JAD-141890] [PMID: 25261448]
[104]
Kim T, Yang HY, Park BG, Jung SY, Park J-H, Park KD, et al. Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer’s disease. Eur J Med Chem 125: 1172-92. (2017).
[http://dx.doi.org/10.1016/j.ejmech.2016.11.017] [PMID: 27855359]
[105]
Gruia MI, Negoita V, Vasilescu M, Panait M, Gruia I, Velescu BS, et al. Biochemical action of new complexes of ruthenium with quinolones as potential antitumor agents. Anticancer Res 35(6): 3371-8. (2015).
[PMID: 26026097]
[106]
Carayon P, Portier M, Dussossoy D, Bord A, Petitprêtre G, Canat X, et al. Involvement of peripheral benzodiazepine receptors in the protection of hematopoietic cells against oxygen radical damage. Blood 87(8): 3170-8. (1996).
[http://dx.doi.org/10.1182/blood.V87.8.3170.bloodjournal8783170] [PMID: 8605331]
[107]
Wang M, Wang X, Zhao L, Ma W, Rodriguez IR, Fariss RN, et al. Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina. J Neurosci 34(10): 3793-806. (2014).
[http://dx.doi.org/10.1523/JNEUROSCI.3153-13.2014] [PMID: 24599476]
[108]
Repalli J. Translocator protein (TSPO) role in aging and Alzheimer’s disease. Curr Aging Sci 7(3): 168-75. (2014).
[http://dx.doi.org/10.2174/1874609808666141210103146] [PMID: 25495567]
[109]
Hansson CA, Frykman S, Farmery MR, Tjernberg LO, Nilsberth C, Pursglove SE, et al. Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria. J Biol Chem 279(49): 51654-60. (2004).
[http://dx.doi.org/10.1074/jbc.M404500200] [PMID: 15456764]
[110]
Ohyagi Y, Yamada T, Nishioka K, Clarke NJ, Tomlinson AJ, Naylor S, et al. Selective increase in cellular A beta 42 is related to apoptosis but not necrosis. Neuroreport 11(1): 167-71. (2000).
[http://dx.doi.org/10.1097/00001756-200001170-00033] [PMID: 10683851]
[111]
Casley CS, Canevari L, Land JM, Clark JB, Sharpe MA. Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem 80(1): 91-100. (2002).
[http://dx.doi.org/10.1046/j.0022-3042.2001.00681.x] [PMID: 11796747]
[112]
Yan SD, Stern DM. Mitochondrial dysfunction and Alzheimer’s disease: role of amyloid-beta peptide alcohol dehydrogenase (ABAD). Int J Exp Pathol 86(3): 161-71. (2005).
[http://dx.doi.org/10.1111/j.0959-9673.2005.00427.x] [PMID: 15910550]
[113]
Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 304(5669): 448-52. (2004).
[http://dx.doi.org/10.1126/science.1091230] [PMID: 15087549]
[114]
Li F, Calingasan NY, Yu F, Mauck WM, Toidze M, Almeida CG, et al. Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J Neurochem 89(5): 1308-12. (2004).
[http://dx.doi.org/10.1111/j.1471-4159.2004.02455.x] [PMID: 15147524]
[115]
Tu LN, Zhao AH, Hussein M, Stocco DM, Selvaraj V. Translocator protein (TSPO) affects mitochondrial fatty acid oxidation in steroidogenic cells. Endocrinology 157(3): 1110-21. (2016).
[http://dx.doi.org/10.1210/en.2015-1795] [PMID: 26741196]
[116]
Biswas L, Zhou X, Dhillon B, Graham A, Shu X. Retinal pigment epithelium cholesterol efflux mediated by the 18 kDa translocator protein, TSPO, a potential target for treating age-related macular degeneration. Hum Mol Genet 26(22): 4327-39. (2017).
[http://dx.doi.org/10.1093/hmg/ddx319] [PMID: 28973423]
[117]
Santoro A, Mattace Raso G, Taliani S, Da Pozzo E, Simorini F, Costa B, et al. TSPO-ligands prevent oxidative damage and inflammatory response in C6 glioma cells by neurosteroid synthesis. Eur J Pharm Sci 88: 124-31. (2016).
[http://dx.doi.org/10.1016/j.ejps.2016.04.006] [PMID: 27094781]

Rights & Permissions Print Cite
Article Metrics
24
1
© 2024 Bentham Science Publishers | Privacy Policy