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

CREB：阿尔茨海默氏病的多方面靶标

卷 17, 期 14, 2020

页: [1280 - 1293] 页: 14

弟呕挨: 10.2174/1567205018666210218152253

价格: $65

摘要

阿尔茨海默氏病（AD）是一种持续的神经病理性疾病，表现为神经元/突触死亡，老年斑形成，过度磷酸化的tau缠结，神经炎症和凋亡性细胞死亡。尚无针对AD的治疗突破继续寻求合适的干预措施。除各种候选药物外，环状AMP蛋白激酶A-cAMP反应元件结合蛋白（cAMP / PKA / CREB）途径是最受欢迎的药物靶点AD，因为大量质量文献证明cAMP信号传导和CREB的下调介导的AD转录级联反应。 cAMP信号在进化上是保守的，可以在所有物种中发现。 cAMP反应元件结合蛋白（CREB）是一种普遍存在的且整体表达清晰的转录方式，可调节神经元的生长，神经元的分化/增殖，突触可塑性，神经发生，神经元的成熟，空间记忆，长期记忆的形成以及确保神经元的存活。 CREB是分子机制的核心部分，在将短期记忆转化为长期记忆中发挥作用。除AD以外，CREB信号的损伤在成瘾，帕金森氏症，精神分裂症，亨廷顿舞蹈病，缺氧，预适应作用，局部缺血，酒精中毒，焦虑和抑郁症中也有很好的记录。当前的工作强调了CREB介导的转录信号转导对AD的主要病理标志（淀粉样蛋白β，神经元丢失，炎症，细胞凋亡等）的作用和影响。目前的工作证明了不断的努力来探索CREB及其相关下游信号通路在认知缺陷和神经退行性并发症（尤其是AD）中的多维作用。此外，可以肯定的是，环状核苷酸信号可能具有巨大的潜力来治疗神经退行性并发症，例如AD。

关键词: 阿尔茨海默氏病，cAMP反应元件结合蛋白（CREB），PKA，cAMP，神经退行性疾病，淀粉样β蛋白。

« Previous Next »
[1]
James BD, Bennett DA. Causes and patterns of dementia: An update in the era of redefining Alzheimer’s disease. Annu Rev Public Health 2019; 40: 65-84.
[http://dx.doi.org/10.1146/annurev-publhealth-040218-043758] [PMID: 30642228]
[2]
Sharma VK, Singh TG. Navigating Alzheimer’s disease via chronic stress: The role of glucocorticoids. Curr Drug Targets 2020; 21(5): 433-44.
[http://dx.doi.org/10.2174/1389450120666191017114735] [PMID: 31625472]
[3]
Zhao J, Zhang G, Li M, Luo Q, Leng Y, Liu X. Neuro-protective effects of aloperine in an Alzheimer’s disease cellular model. Biomed Pharmacother 2018; 108: 137-43.
[http://dx.doi.org/10.1016/j.biopha.2018.09.008] [PMID: 30218858]
[4]
Peterson AC, Li CR. Noradrenergic dysfunction in Alzheimer’s and Parkinson’s diseases-an overview of imaging studies. Front Aging Neurosci 2018; 10: 127.
[http://dx.doi.org/10.3389/fnagi.2018.00127] [PMID: 29765316]
[5]
Sharma VK, Mehta V, Singh TG. Alzheimer’s disorder: Epigenetic connection and associated risk factors. Curr Neuropharmacol 2020; 18(8): 740-53.
[http://dx.doi.org/10.2174/1570159X18666200128125641] [PMID: 31989902]
[6]
Razgonova MP, Veselov VV, Zakharenko AM, et al. Panax ginseng components and the pathogenesis of Alzheimer’s disease. Mol Med Rep 2019; 19(4): 2975-98.
[http://dx.doi.org/10.3892/mmr.2019.9972] [PMID: 30816465]
[7]
Barker WW, Luis CA, Kashuba A, et al. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc Disord 2002; 16(4): 203-12.
[http://dx.doi.org/10.1097/00002093-200210000-00001] [PMID: 12468894]
[8]
Thompson S, Lanctôt KL, Herrmann N. The benefits and risks associated with cholinesterase inhibitor therapy in Alzheimer’s disease. Expert Opin Drug Saf 2004; 3(5): 425-40.
[http://dx.doi.org/10.1517/14740338.3.5.425] [PMID: 15335298]
[9]
Cummings J, Lee G, Ritter A, Zhong K. Alzheimer’s disease drug development pipeline: 2018. Alzheimers Dement 2018; 4: 195-214.
[http://dx.doi.org/10.1016/j.trci.2018.03.009] [PMID: 29955663]
[10]
Bae HJ, Sowndhararajan K, Park HB, et al. Danshensu attenuates scopolamine and amyloid-β-induced cognitive impairments through the activation of PKA-CREB signaling in mice. Neurochem Int 2019; 131104537
[http://dx.doi.org/10.1016/j.neuint.2019.104537] [PMID: 31425745]
[11]
De Roeck EE, De Deyn PP, Dierckx E, Engelborghs S. Brief cognitive screening instruments for early detection of Alzheimer’s disease: A systematic review. Alzheimers Res Ther 2019; 11(1): 21.
[http://dx.doi.org/10.1186/s13195-019-0474-3] [PMID: 30819244]
[12]
Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: A systematic review and meta-analysis. Lancet Neurol 2016; 15(7): 673-84.
[http://dx.doi.org/10.1016/S1474-4422(16)00070-3] [PMID: 27068280]
[13]
Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science 2002; 298(5594): 789-91.
[http://dx.doi.org/10.1126/science.1074069] [PMID: 12399581]
[14]
Morris GP, Clark IA, Vissel B. Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer’s disease. Acta Neuropathol Commun 2014; 2: 135.
[http://dx.doi.org/10.1186/s40478-014-0135-5] [PMID: 25231068]
[15]
Sharma VK, Singh TG, Singh S. Cyclic Nucleotides signaling and phosphodiesterase inhibition: Defying Alzheimer’s disease. Curr Drug Targets 2020; 21(13): 1371-84.
[http://dx.doi.org/10.2174/1389450121666200727104728] [PMID: 32718286]
[16]
Acquarone E, Argyrousi EK, van den Berg M, et al. Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade. Mol Neurodegener 2019; 14(1): 26.
[http://dx.doi.org/10.1186/s13024-019-0326-4] [PMID: 31248451]
[17]
Liang Z, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX. Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain. J Neurochem 2007; 103(6): 2462-70.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04942.x] [PMID: 17908236]
[18]
De Felice FG, Wasilewska-Sampaio AP, Barbosa AC, Gomes FC, Klein WL, Ferreira ST. Cyclic AMP enhancers and Abeta oligomerization blockers as potential therapeutic agents in Alzheimer’s disease. Curr Alzheimer Res 2007; 4(3): 263-71.
[http://dx.doi.org/10.2174/156720507781077287] [PMID: 17627483]
[19]
Wang A, Bibb JA. Is CREB the angry bird that releases memory in Alzheimer’s? Neuropsychopharmacology 2011; 36(11): 2153-4.
[http://dx.doi.org/10.1038/npp.2011.126] [PMID: 21918517]
[20]
España J, Valero J, Miñano-Molina AJ, et al. Beta-Amyloid disrupts activity-dependent gene transcription required for memory through the CREB coactivator CRTC1. J Neurosci 2010; 30(28): 9402-10.
[http://dx.doi.org/10.1523/JNEUROSCI.2154-10.2010] [PMID: 20631169]
[21]
Bartolotti N, Bennett DA, Lazarov O. Reduced pCREB in Alzheimer’s disease prefrontal cortex is reflected in peripheral blood mononuclear cells. Mol Psychiatry 2016; 21(9): 1158-66.
[http://dx.doi.org/10.1038/mp.2016.111] [PMID: 27480489]
[22]
Sharma VK, Singh TG. Insulin resistance and bioenergetic manifestations: Targets and approaches in Alzheimer’s disease. Life Sci 2020; 262118401
[http://dx.doi.org/10.1016/j.lfs.2020.118401] [PMID: 32926928]
[23]
Yan K, Gao LN, Cui YL, Zhang Y, Zhou X. The cyclic AMP signaling pathway: Exploring targets for successful drug discovery.(Review) Mol Med Rep 2016; 13(5): 3715-23.
[http://dx.doi.org/10.3892/mmr.2016.5005] [PMID: 27035868]
[24]
Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 2005; 85(4): 1303-42.
[http://dx.doi.org/10.1152/physrev.00001.2005] [PMID: 16183914]
[25]
Lonze BE, Ginty DD. Function and regulation of CREB family transcription factors in the nervous system. Neuron 2002; 35(4): 605-23.
[http://dx.doi.org/10.1016/S0896-6273(02)00828-0] [PMID: 12194863]
[26]
Choi J, Levey AI, Weintraub ST, et al. Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson’s and Alzheimer’s diseases. J Biol Chem 2004; 279(13): 13256-64.
[http://dx.doi.org/10.1074/jbc.M314124200] [PMID: 14722078]
[27]
Montminy MR, Sevarino KA, Wagner JA, Mandel G, Goodman RH. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci USA 1986; 83(18): 6682-6.
[http://dx.doi.org/10.1073/pnas.83.18.6682] [PMID: 2875459]
[28]
Silva AJ, Kogan JH, Frankland PW, Kida S. CREB and memory. Annu Rev Neurosci 1998; 21: 127-48.
[http://dx.doi.org/10.1146/annurev.neuro.21.1.127] [PMID: 9530494]
[29]
Chen Y, Huang X, Zhang YW, et al. Alzheimer’s β-secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-amyloid. J Neurosci 2012; 32(33): 11390-5.
[http://dx.doi.org/10.1523/JNEUROSCI.0757-12.2012] [PMID: 22895721]
[30]
Cadd G, McKnight GS. Distinct patterns of cAMP-dependent protein kinase gene expression in mouse brain. Neuron 1989; 3(1): 71-9.
[http://dx.doi.org/10.1016/0896-6273(89)90116-5] [PMID: 2619996]
[31]
Chang A, Li PP, Warsh JJ. Altered cAMP-dependent protein kinase subunit immunolabeling in post-mortem brain from patients with bipolar affective disorder. J Neurochem 2003; 84(4): 781-91.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01605.x] [PMID: 12562522]
[32]
Landeira BS, Santana TTDS, Araújo JAM, et al. Activity-independent effects of CREB on neuronal survival and differentiation during mouse cerebral cortex development. Cereb Cortex 2018; 28(2): 538-48.
[PMID: 27999124]
[33]
Ortega-Martínez S. A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis. Front Mol Neurosci 2015; 8: 46.
[http://dx.doi.org/10.3389/fnmol.2015.00046] [PMID: 26379491]
[34]
Mayr B, Montminy M. Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2001; 2(8): 599-609.
[http://dx.doi.org/10.1038/35085068] [PMID: 11483993]
[35]
Delghandi MP, Johannessen M, Moens U. The cAMP signalling pathway activates CREB through PKA, p38 and MSK1 in NIH 3T3 cells. Cell Signal 2005; 17(11): 1343-51.
[http://dx.doi.org/10.1016/j.cellsig.2005.02.003] [PMID: 16125054]
[36]
Shaywitz AJ, Greenberg ME. CREB: A stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 1999; 68: 821-61.
[http://dx.doi.org/10.1146/annurev.biochem.68.1.821] [PMID: 10872467]
[37]
Sun P, Enslen H, Myung PS, Maurer RA. Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity. Genes Dev 1994; 8(21): 2527-39.
[http://dx.doi.org/10.1101/gad.8.21.2527] [PMID: 7958915]
[38]
Riccio A, Alvania RS, Lonze BE, et al. A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol Cell 2006; 21(2): 283-94.
[http://dx.doi.org/10.1016/j.molcel.2005.12.006] [PMID: 16427017]
[39]
Fujino H, Kitaoka Y, Hayashi Y, et al. Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-alpha-induced optic nerve degeneration. Acta Neuropathol 2009; 117(1): 75-84.
[http://dx.doi.org/10.1007/s00401-008-0440-9] [PMID: 18830614]
[40]
Steven A, Seliger B. Control of CREB expression in tumors: From molecular mechanisms and signal transduction pathways to therapeutic target. Oncotarget 2016; 7(23): 35454-65.
[http://dx.doi.org/10.18632/oncotarget.7721] [PMID: 26934558]
[41]
Dawson TM, Ginty DD. CREB family transcription factors inhibit neuronal suicide. Nat Med 2002; 8(5): 450-1.
[http://dx.doi.org/10.1038/nm0502-450] [PMID: 11984583]
[42]
Mantamadiotis T, Lemberger T, Bleckmann SC, et al. Disruption of CREB function in brain leads to neurodegeneration. Nat Genet 2002; 31(1): 47-54.
[http://dx.doi.org/10.1038/ng882] [PMID: 11967539]
[43]
Sekeres MJ, Neve RL, Frankland PW, Josselyn SA. Dorsal hippocampal CREB is both necessary and sufficient for spatial memory. Learn Mem 2010; 17(6): 280-3.
[http://dx.doi.org/10.1101/lm.1785510] [PMID: 20495061]
[44]
Chen G, Zou X, Watanabe H, van Deursen JM, Shen J. CREB binding protein is required for both short-term and long-term memory formation. J Neurosci 2010; 30(39): 13066-77.
[http://dx.doi.org/10.1523/JNEUROSCI.2378-10.2010] [PMID: 20881124]
[45]
Saura CA, Cardinaux JR. Emerging roles of CREB-regulated transcription coactivators in brain physiology and pathology. Trends Neurosci 2017; 40(12): 720-33.
[http://dx.doi.org/10.1016/j.tins.2017.10.002] [PMID: 29097017]
[46]
Ch’ng TH, Uzgil B, Lin P, Avliyakulov NK, O’Dell TJ, Martin KC. Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus. Cell 2012; 150(1): 207-21.
[http://dx.doi.org/10.1016/j.cell.2012.05.027] [PMID: 22770221]
[47]
Ch’ng TH, DeSalvo M, Lin P, Vashisht A, Wohlschlegel JA, Martin KC. Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons. Front Mol Neurosci 2015; 8: 48.
[http://dx.doi.org/10.3389/fnmol.2015.00048] [PMID: 26388727]
[48]
Nonaka M, Kim R, Fukushima H, et al. Region-specific activation of CRTC1-CREB signaling mediates long-term fear memory. Neuron 2014; 84(1): 92-106.
[http://dx.doi.org/10.1016/j.neuron.2014.08.049] [PMID: 25277455]
[49]
Parra-Damas A, Chen M, Enriquez-Barreto L, et al. CRTC1 function during memory encoding is disrupted in neurodegeneration. Biol Psychiatry 2017; 81(2): 111-23.
[http://dx.doi.org/10.1016/j.biopsych.2016.06.025] [PMID: 27587263]
[50]
Uchida S, Teubner BJW, Hevi C, et al. CRTC1 nuclear translocation following learning modulates memory strength via exchange of chromatin remodeling complexes on the Fgf1 gene. Cell Rep 2017; 18(2): 352-66.
[http://dx.doi.org/10.1016/j.celrep.2016.12.052] [PMID: 28076781]
[51]
Hirano Y, Ihara K, Masuda T, et al. Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies. Nat Commun 2016; 7: 13471.
[http://dx.doi.org/10.1038/ncomms13471] [PMID: 27841260]
[52]
Hirano Y, Masuda T, Naganos S, et al. Fasting launches CRTC to facilitate long-term memory formation in Drosophila. Science 2013; 339(6118): 443-6.
[http://dx.doi.org/10.1126/science.1227170] [PMID: 23349290]
[53]
Sekeres MJ, Mercaldo V, Richards B, et al. Increasing CRTC1 function in the dentate gyrus during memory formation or reactivation increases memory strength without compromising memory quality. J Neurosci 2012; 32(49): 17857-68.
[http://dx.doi.org/10.1523/JNEUROSCI.1419-12.2012] [PMID: 23223304]
[54]
Kovács KA, Steullet P, Steinmann M, et al. TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity. Proc Natl Acad Sci USA 2007; 104(11): 4700-5.
[http://dx.doi.org/10.1073/pnas.0607524104] [PMID: 17360587]
[55]
Mendioroz M, Celarain N, Altuna M, et al. CRTC1 gene is differentially methylated in the human hippocampus in Alzheimer’s disease. Alzheimers Res Ther 2016; 8(1): 15.
[http://dx.doi.org/10.1186/s13195-016-0183-0] [PMID: 27094739]
[56]
Parra-Damas A, Valero J, Chen M, et al. Crtc1 activates a transcriptional program deregulated at early Alzheimer’s disease-related stages. J Neurosci 2014; 34(17): 5776-87.
[http://dx.doi.org/10.1523/JNEUROSCI.5288-13.2014] [PMID: 24760838]
[57]
Wilson EN, Abela AR, Do Carmo S, et al. Intraneuronal amyloid beta accumulation disrupts hippocampal CRTC1-dependent gene expression and cognitive function in a rat model of Alzheimer disease. Cereb Cortex 2017; 27(2): 1501-11.
[PMID: 26759481]
[58]
España J, Valero J, Miñano-Molina AJ, et al. β-Amyloid disrupts activity-dependent gene transcription required for memory through the CREB coactivator CRTC1. J Neurosci 2010; 30(28): 9402-10.
[http://dx.doi.org/10.1523/JNEUROSCI.2154-10.2010] [PMID: 20631169]
[59]
Moon M, Jung ES, Jeon SG, et al. Nurr1 (NR4A2) regulates Alzheimer’s disease-related pathogenesis and cognitive function in the 5XFAD mouse model. Aging Cell 2019; 18(1)e12866
[http://dx.doi.org/10.1111/acel.12866] [PMID: 30515963]
[60]
Chen A, Muzzio IA, Malleret G, et al. Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins. Neuron 2003; 39(4): 655-69.
[http://dx.doi.org/10.1016/S0896-6273(03)00501-4] [PMID: 12925279]
[61]
Pasini S, Corona C, Liu J, Greene LA, Shelanski ML. Specific downregulation of hippocampal ATF4 reveals a necessary role in synaptic plasticity and memory. Cell Rep 2015; 11(2): 183-91.
[http://dx.doi.org/10.1016/j.celrep.2015.03.025] [PMID: 25865882]
[62]
Lai KO, Zhao Y, Ch’ng TH, Martin KC. Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons. Proc Natl Acad Sci USA 2008; 105(44): 17175-80.
[http://dx.doi.org/10.1073/pnas.0803906105] [PMID: 18957537]
[63]
Baleriola J, Walker CA, Jean YY, et al. Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions. Cell 2014; 158(5): 1159-72.
[http://dx.doi.org/10.1016/j.cell.2014.07.001] [PMID: 25171414]
[64]
Segev Y, Barrera I, Ounallah-Saad H, et al. PKR inhibition rescues memory deficit and ATF4 oerexpression in ApoE ε4 human replacement mice. J Neurosci 2015; 35(38): 12986-93.
[http://dx.doi.org/10.1523/JNEUROSCI.5241-14.2015] [PMID: 26400930]
[65]
Parra-Damas A, Saura CA. Synapse to nucleus signaling in neurodegenerative and neuropsychiatric disorders. Biol Psychiatry 2019; 86(2): 87-96.
[66]
Rudolph D, Tafuri A, Gass P, Hämmerling GJ, Arnold B, Schütz G. Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein. Proc Natl Acad Sci USA 1998; 95(8): 4481-6.
[http://dx.doi.org/10.1073/pnas.95.8.4481] [PMID: 9539763]
[67]
Ao H, Ko SW, Zhuo M. CREB activity maintains the survival of cingulate cortical pyramidal neurons in the adult mouse brain. Mol Pain 2006; 2: 15.
[http://dx.doi.org/10.1186/1744-8069-2-15] [PMID: 16640787]
[68]
Sakamoto K, Karelina K, Obrietan K. CREB: A multifaceted regulator of neuronal plasticity and protection. J Neurochem 2011; 116(1): 1-9.
[http://dx.doi.org/10.1111/j.1471-4159.2010.07080.x] [PMID: 21044077]
[69]
Delhaye S, Bardoni B. Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders. Mol Psychiatry 2021.
[http://dx.doi.org/10.1038/s41380-020-00997-9] [PMID: 33414502]
[70]
Cowburn RF, O’Neill C, Ravid R, Alafuzoff I, Winblad B, Fowler CJ. Adenylyl cyclase activity in postmortem human brain: evidence of altered G protein mediation in Alzheimer’s disease. J Neurochem 1992; 58(4): 1409-19.
[http://dx.doi.org/10.1111/j.1471-4159.1992.tb11357.x] [PMID: 1548475]
[71]
Wang HY, Pisano MR, Friedman E. Attenuated protein kinase C activity and translocation in Alzheimer’s disease brain. Neurobiol Aging 1994; 15(3): 293-8.
[http://dx.doi.org/10.1016/0197-4580(94)90023-X] [PMID: 7936052]
[72]
Lahiri DK, Ge YW, Rogers JT, Kumar S, Greig NH, Maloney B. Taking down the unindicted co-conspirators of amyloid peptide mediated neuronal death: Shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factors. Curr Alzheimer Res 2006; 3: 475-83.
[http://dx.doi.org/10.2174/156720506779025224] [PMID: 17168646]
[73]
Alausa A, Ogundepo S, Olaleke B, Adeyemi R, Olatinwo M, Ismail A. Chinese nutraceuticals and physical activity; their role in neurodegenerative tauopathies. Chin Med 2021; 16(1): 1.
[http://dx.doi.org/10.1186/s13020-020-00418-7] [PMID: 33407732]
[74]
Guzowski JF, Timlin JA, Roysam B, McNaughton BL, Worley PF, Barnes CA. Mapping behaviorally relevant neural circuits with immediate-early gene expression. Curr Opin Neurobiol 2005; 15(5): 599-606.
[http://dx.doi.org/10.1016/j.conb.2005.08.018] [PMID: 16150584]
[75]
Didier S, Sauvé F, Domise M, Buée L, Marinangeli C, Vingtdeux V. AMP-activated protein kinase controls immediate early genes expression following synaptic activation through the PKA/CREB pathway. Int J Mol Sci 2018; 19(12): 3716.
[http://dx.doi.org/10.3390/ijms19123716] [PMID: 30467274]
[76]
Sheng C, Xu P, Zhou K, Deng D, Zhang C, Wang Z. Icariin attenuates synaptic and cognitive deficits in an Aβ1–42-induced rat model of Alzheimer’s disease. BioMed Res Int 2017; 20177464872
[77]
Um HS, Kang EB, Koo JH, et al. Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer’s disease. Neurosci Res 2011; 69(2): 161-73.
[http://dx.doi.org/10.1016/j.neures.2010.10.004] [PMID: 20969897]
[78]
Scott Bitner R. Cyclic AMP response element-binding protein (CREB) phosphorylation: a mechanistic marker in the development of memory enhancing Alzheimer’s disease therapeutics. Biochem Pharmacol 2012; 83(6): 705-14.
[http://dx.doi.org/10.1016/j.bcp.2011.11.009] [PMID: 22119240]
[79]
Yang JL, Lin YT, Chuang PC, Bohr VA, Mattson MP. BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. Neuromolecular Med 2014; 16(1): 161-74.
[http://dx.doi.org/10.1007/s12017-013-8270-x] [PMID: 24114393]
[80]
Hu YS, Long N, Pigino G, Brady ST, Lazarov O. Molecular mechanisms of environmental enrichment: impairments in Akt/GSK3β, neurotrophin-3 and CREB signaling. PLoS One 2013; 8(5)e64460
[http://dx.doi.org/10.1371/journal.pone.0064460] [PMID: 23700479]
[81]
Amidfar M, de Oliveira J, Kucharska E, Budni J, Kim YK. The role of CREB and BDNF in neurobiology and treatment of Alzheimer’s disease. Life Sci 2020; 257118020
[http://dx.doi.org/10.1016/j.lfs.2020.118020] [PMID: 32603820]
[82]
Jin N, Qian W, Yin X, et al. CREB regulates the expression of neuronal glucose transporter 3: a possible mechanism related to impaired brain glucose uptake in Alzheimer’s disease. Nucleic Acids Res 2013; 41(5): 3240-56.
[http://dx.doi.org/10.1093/nar/gks1227] [PMID: 23341039]
[83]
Yang H, Yang L. Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy. J Mol Endocrinol 2016; 57(2): R93-R108.
[http://dx.doi.org/10.1530/JME-15-0316] [PMID: 27194812]
[84]
Yu S, Cheng Q, Li L, Liu M, Yang Y, Ding F. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside confers neuroprotection in cell and animal models of ischemic stroke through calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3. Toxicol Appl Pharmacol 2014; 277(3): 259-69.
[http://dx.doi.org/10.1016/j.taap.2014.03.025] [PMID: 24726522]
[85]
Yan T, He B, Xu M. Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element binding signaling pathway. Phytother Res 2019; 33(4): 1065-73.
[86]
Pugazhenthi S, Nesterova A, Jambal P, et al. Oxidative stress-mediated down-regulation of bcl-2 promoter in hippocampal neurons. J Neurochem 2003; 84(5): 982-96.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01606.x] [PMID: 12603823]
[87]
Gong P, Stewart D, Hu B, Vinson C, Alam J. Multiple basic-leucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite. Arch Biochem Biophys 2002; 405(2): 265-74.
[http://dx.doi.org/10.1016/S0003-9861(02)00404-6] [PMID: 12220541]
[88]
Kim TS, Kawaguchi M, Suzuki M, et al. The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxidative stress. Dis Model Mech 2010; 3(11-12): 752-62.
[http://dx.doi.org/10.1242/dmm.004689] [PMID: 20876357]
[89]
Herzig S, Long F, Jhala US, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 2001; 413(6852): 179-83.
[http://dx.doi.org/10.1038/35093131] [PMID: 11557984]
[90]
Pugazhenthi S, Wang M, Pham S, Sze CI, Eckman CB. Downregulation of CREB expression in Alzheimer’s brain and in Aβ-treated rat hippocampal neurons. Mol Neurodegener 2011; 6: 60.
[91]
Nieto R, Kukuljan M, Silva H. BDNF and schizophrenia: From neurodevelopment to neuronal plasticity, learning, and memory. Front Psychiatry 2013; 4: 45.
[http://dx.doi.org/10.3389/fpsyt.2013.00045] [PMID: 23785335]
[92]
Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 1998; 20(4): 709-26.
[http://dx.doi.org/10.1016/S0896-6273(00)81010-7] [PMID: 9581763]
[93]
Palomino A, Vallejo-Illarramendi A, González-Pinto A, et al. Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients. Schizophr Res 2006; 86(1-3): 321-2.
[http://dx.doi.org/10.1016/j.schres.2006.05.028] [PMID: 16829047]
[94]
Pizzorusso T, Ratto GM, Putignano E, Maffei L. Brain-derived neurotrophic factor causes cAMP response element-binding protein phosphorylation in absence of calcium increases in slices and cultured neurons from rat visual cortex. J Neurosci 2000; 20(8): 2809-16.
[http://dx.doi.org/10.1523/JNEUROSCI.20-08-02809.2000] [PMID: 10751432]
[95]
Sciesielski LK, Paliege A, Martinka P, Scholz H. Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats is associated with increased acetylcholine-induced airway contractility. Acta Physiol (Oxf) 2009; 197(3): 253-64.
[http://dx.doi.org/10.1111/j.1748-1716.2009.02016.x] [PMID: 19583705]
[96]
Sen NER. Stress, CREB, and memory: A tangled emerging link in disease. Neuroscientist 2019; 25(5): 420-33.
[http://dx.doi.org/10.1177/1073858418816611] [PMID: 30477403]
[97]
Mattson MP, Duan W. Apoptotic biochemical cascades in synaptic compartments: roles in adaptive plasticity and neurodegenerative disorders. J Neurosci Res 1999; 58(1): 152-66.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19991001)58:1<152:AID-JNR15>3.0.CO;2-V] [PMID: 10491580]
[98]
Roth KA. Caspases, apoptosis, and Alzheimer disease: Causation, correlation, and confusion. J Neuropathol Exp Neurol 2001; 60(9): 829-38.
[http://dx.doi.org/10.1093/jnen/60.9.829] [PMID: 11556539]
[99]
Rissman RA, Poon WW, Blurton-Jones M, et al. Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. J Clin Invest 2004; 114(1): 121-30.
[http://dx.doi.org/10.1172/JCI200420640] [PMID: 15232619]
[100]
Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 2000; 1(2): 120-9.
[http://dx.doi.org/10.1038/35040009] [PMID: 11253364]
[101]
Guan R, Lv J, Xiao F, Tu Y, Xie Y, Li L. Potential role of the cAMP/PKA/CREB signalling pathway in hypoxic preconditioning and effect on propofol-induced neurotoxicity in the hippocampus of neonatal rats. Mol Med Rep 2019; 20(2): 1837-45.
[http://dx.doi.org/10.3892/mmr.2019.10397] [PMID: 31257533]
[102]
Ryu H, Lee J, Impey S, Ratan RR, Ferrante RJ. Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons. Proc Natl Acad Sci USA 2005; 102(39): 13915-20.
[http://dx.doi.org/10.1073/pnas.0502878102] [PMID: 16169904]
[103]
Ma L, Xiao H, Wen J, Liu Z, He Y, Yuan F. Possible mechanism of Vitis vinifera L. flavones on neurotransmitters, synaptic transmission and related learning and memory in Alzheimer model rats. Lipids Health Dis 2018; 17(1): 152.
[http://dx.doi.org/10.1186/s12944-018-0708-6] [PMID: 29973282]
[104]
Smith DL, Pozueta J, Gong B, Arancio O, Shelanski M. Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proc Natl Acad Sci USA 2009; 106(39): 16877-82.
[http://dx.doi.org/10.1073/pnas.0908706106] [PMID: 19805389]
[105]
Dineley KT, Westerman M, Bui D, Bell K, Ashe KH, Sweatt JD. Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer’s disease. J Neurosci 2001; 21(12): 4125-33.
[http://dx.doi.org/10.1523/JNEUROSCI.21-12-04125.2001] [PMID: 11404397]
[106]
Du H, Guo L, Wu X, et al. Cyclophilin D deficiency rescues Aβ-impaired PKA/CREB signaling and alleviates synaptic degeneration. Biochim Biophys Acta 2014; 1842(12 Pt A): 2517-27.
[http://dx.doi.org/10.1016/j.bbadis.2013.03.004] [PMID: 23507145]
[107]
Singh S, Singh TG. Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: An mechanistic approach. Curr Neuropharmacol 2020; 18(10): 918-35.
[http://dx.doi.org/10.2174/1570159X18666200207120949] [PMID: 32031074]
[108]
Sharma VK, Goyal A, Subhrahmanya G. Tau A friend turns Foe. Int J Pharm Sci Rev Res 2010; 1(1): 21-7.
[109]
Liu H, Jin X, Yin X, Jin N, Liu F, Qian W. PKA-CREB signaling suppresses tau transcription. J Alzheimers Dis 2015; 46(1): 239-48.
[http://dx.doi.org/10.3233/JAD-142610] [PMID: 25720403]
[110]
Herold S, Jagasia R, Merz K, Wassmer K, Lie DC. CREB signalling regulates early survival, neuronal gene expression and morphological development in adult subventricular zone neurogenesis. Mol Cell Neurosci 2011; 46(1): 79-88.
[http://dx.doi.org/10.1016/j.mcn.2010.08.008] [PMID: 20801218]
[111]
Gundersen BB, Briand LA, Onksen JL, Lelay J, Kaestner KH, Blendy JA. Increased hippocampal neurogenesis and accelerated response to antidepressants in mice with specific deletion of CREB in the hippocampus: Role of cAMP response-element modulator τ. J Neurosci 2013; 33(34): 13673-85.
[http://dx.doi.org/10.1523/JNEUROSCI.1669-13.2013] [PMID: 23966689]
[112]
Jagasia R, Steib K, Englberger E, et al. GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus. J Neurosci 2009; 29(25): 7966-77.
[http://dx.doi.org/10.1523/JNEUROSCI.1054-09.2009] [PMID: 19553437]
[113]
Cameron HA, Glover LR. Adult neurogenesis: Beyond learning and memory. Annu Rev Psychol 2015; 66: 53-81.
[http://dx.doi.org/10.1146/annurev-psych-010814-015006] [PMID: 25251485]
[114]
Luo Y, Kuang S, Li H, Ran D, Yang J. cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress. Oncotarget 2017; 8(22): 35558-72.
[http://dx.doi.org/10.18632/oncotarget.16009] [PMID: 28415673]
[115]
Ben-Ari Y. Excitatory actions of gaba during development: The nature of the nurture. Nat Rev Neurosci 2002; 3(9): 728-39.
[http://dx.doi.org/10.1038/nrn920] [PMID: 12209121]
[116]
Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H. GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 2006; 439(7076): 589-93.
[http://dx.doi.org/10.1038/nature04404] [PMID: 16341203]
[117]
Fusco S, Leone L, Barbati SA, et al. A CREB-Sirt1-Hes1 circuitry mediates Neural stem cell response to glucose availability. Cell Rep 2016; 14(5): 1195-205.
[http://dx.doi.org/10.1016/j.celrep.2015.12.092] [PMID: 26804914]
[118]
Bartolome F, de la Cueva M, Pascual C, et al. Amyloid β-induced impairments on mitochondrial dynamics, hippocampal neurogenesis, and memory are restored by phosphodiesterase 7 inhibition. Alzheimers Res Ther 2018; 10(1): 24.
[http://dx.doi.org/10.1186/s13195-018-0352-4] [PMID: 29458418]
[119]
Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol 2014; 14(7): 463-77.
[http://dx.doi.org/10.1038/nri3705] [PMID: 24962261]
[120]
Mosenden R, Taskén K. Cyclic AMP-mediated immune regulation--overview of mechanisms of action in T cells. Cell Signal 2011; 23(6): 1009-16.
[http://dx.doi.org/10.1016/j.cellsig.2010.11.018] [PMID: 21130867]
[121]
Gräff J, Mansuy IM. Epigenetic dysregulation in cognitive disorders. Eur J Neurosci 2009; 30(1): 1-8.
[http://dx.doi.org/10.1111/j.1460-9568.2009.06787.x] [PMID: 19508697]
[122]
Delgado-Morales R, Agís-Balboa RC, Esteller M, Berdasco M. Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders. Clin Epigenetics 2017; 9: 67.
[http://dx.doi.org/10.1186/s13148-017-0365-z] [PMID: 28670349]
[123]
Zukin S, Epigenetics ZS. Alzheimers Dement 2009; 5: 146-P147.
[http://dx.doi.org/10.1016/j.jalz.2009.05.502]
[124]
Zeng L, Zeng B, Wang H, et al. Microbiota modulates behavior and protein kinase C mediated cAMP response element-binding protein Signaling. Sci Rep 2016; 6: 29998.
[http://dx.doi.org/10.1038/srep29998] [PMID: 27444685]
[125]
Frolinger T, Sims S, Smith C, et al. The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids. Sci Rep 2019; 9(1): 3546.
[http://dx.doi.org/10.1038/s41598-019-39994-6] [PMID: 30837576]
[126]
Yanai S, Endo S. PDE3 Inhibitors repurposed as treatments for age-related cognitive impairment. Mol Neurobiol 2019; 56(6): 4306-16.
[http://dx.doi.org/10.1007/s12035-018-1374-4] [PMID: 30311144]
[127]
Sanders O, Rajagopal L. Phosphodiesterase inhibitors for Alzheimer's Disease: A systematic review of clinical trials and epidemiology with a mechanistic rationale. J Alzheimers dis rep 2020; 4(1): 185-215..
[128]
Bhat A, Ray B, Mahalakshmi AM, et al. Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders. Pharmacol Res 2020; 160105078
[http://dx.doi.org/10.1016/j.phrs.2020.105078] [PMID: 32673703]
[129]
Rehman SU, Ikram M, Ullah N, et al. Neurological enhancement effects of melatonin against brain injury-induced oxidative stress, neuroinflammation, and neurodegeneration via AMPK/CREB signaling. Cells 2019; 8(7): 760.
[http://dx.doi.org/10.3390/cells8070760] [PMID: 31330909]
[130]
Chen X, Gan L. An exercise-induced messenger boosts memory in Alzheimer’s disease. Nat Med 2019; 25(1): 20-1.
[http://dx.doi.org/10.1038/s41591-018-0311-4] [PMID: 30617321]
[131]
Gong B, Vitolo OV, Trinchese F, Liu S, Shelanski M, Arancio O. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. J Clin Invest 2004; 114(11): 1624-34.
[http://dx.doi.org/10.1172/JCI22831] [PMID: 15578094]
[132]
Tchantchou F, Xu Y, Wu Y, Christen Y, Luo Y. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease. FASEB J 2007; 21(10): 2400-8.
[http://dx.doi.org/10.1096/fj.06-7649com] [PMID: 17356006]
[133]
Nguyen TV, Yao M, Pike CJ. Dihydrotestosterone activates CREB signaling in cultured hippocampal neurons. Brain Res 2009; 1298: 1-12.
[http://dx.doi.org/10.1016/j.brainres.2009.08.066] [PMID: 19729001]
[134]
Li N, Liu GT. The novel squamosamide derivative FLZ enhances BDNF/TrkB/CREB signaling and inhibits neuronal apoptosis in APP/PS1 mice. Acta Pharmacol Sin 2010; 31(3): 265-72.
[http://dx.doi.org/10.1038/aps.2010.3] [PMID: 20154710]
[135]
Ashabi G, Ramin M, Azizi P, et al. ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1α levels in Aβ-injected rats. Behav Brain Res 2012; 232(1): 165-73.
[http://dx.doi.org/10.1016/j.bbr.2012.04.006] [PMID: 22510382]
[136]
Lee JE, Song HK, Park MN, Kim SH. Ethanol extract of oldenlandia diffusa herba attenuates scopolamine-induced cognitive impairments in mice via activation of BDNF, P-CREB and inhibition of acetylcholinesterase. Int J Mol Sci 2018; 19: 363.
[http://dx.doi.org/10.3390/ijms19020363]
[137]
Alexaki VI, Fodelianaki G, Neuwirth A, et al. DHEA inhibits acute microglia-mediated inflammation through activation of the TrkA-Akt1/2-CREB-Jmjd3 pathway. Mol Psychiatry 2018; 23(6): 1410-20.
[http://dx.doi.org/10.1038/mp.2017.167] [PMID: 28894299]
[138]
Qin Y, Zhang Y, Tomic I, et al. Ginkgo biloba extract EGb 761 and its specific components elicit protective protein clearance through the autophagy-lysosomal pathway in tau-transgenic mice and cultured neurons. J Alzheimers Dis 2018; 65(1): 243-63.
[http://dx.doi.org/10.3233/JAD-180426] [PMID: 30010136]
[139]
Liu S, Li X, Gao J, Liu Y, Shi J, Gong Q. Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling. Cell Physiol Biochem 2018; 49(3): 985.
[http://dx.doi.org/10.1159/000493232] [PMID: 30196289]
[140]
Li Q, Che HX, Wang CC, et al. Cerebrosides from sea cucumber improved Aβ1-42 -induced cognitive deficiency in a rat model of Alzheimer’s disease. Mol Nutr Food Res 2019; 63(5)e1800707
[PMID: 30512229]

Rights & Permissions Print Cite
Article Metrics
130
2
© 2025 Bentham Science Publishers | Privacy Policy