How an increase in the copy number of HSV-1 during latency can cause Alzheimer's disease: the viral and cellular dynamics according to the microcompetition model.
Alzheimer’s disease
BDNF
BECN1
GABP
HSV-1
Latency
Microcompetition
Mitochondria
NMDA
Neurogenesis
Journal
Journal of neurovirology
ISSN: 1538-2443
Titre abrégé: J Neurovirol
Pays: United States
ID NLM: 9508123
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
28
04
2021
accepted:
16
08
2021
revised:
28
04
2021
pubmed:
13
10
2021
medline:
28
4
2022
entrez:
12
10
2021
Statut:
ppublish
Résumé
Numerous studies observed a link between the herpes smplex virus-1 (HSV-1) and Alzheimer's disease. However, the exact viral and cellular dynamics that lead from an HSV-1 infection to Alzheimer's disease are unknown. In this paper, we use the microcompetition model to formulate these dynamics by connecting seemingly unconnected observations reported in the literature. We concentrate on four pathologies characteristic of Alzheimer's disease. First, we explain how an increase in the copy number of HSV-1 during latency can decrease the expression of BECN1/Beclin1, the degradative trafficking protein, which, in turn, can cause a dysregulation of autophagy and Alzheimer's disease. Second, we show how an increase in the copy number of the latent HSV-1 can decrease the expression of many genes important for mitochondrial genome metabolism, respiratory chain, and homeostasis, which can lead to oxidative stress and neuronal damage, resulting in Alzheimer's disease. Third, we describe how an increase in this copy number can reduce the concentration of the NMDA receptor subunits NR1 and NR2b (Grin1 and Grin2b genes), and brain derived neurotrophic factor (BDNF), which can cause an impaired synaptic plasticity, Aβ accumulation and eventually Alzheimer's disease. Finally, we show how an increase in the copy number of HSV-1 in neural stem/progenitor cells in the hippocampus during the latent phase can lead to an abnormal quantity and quality of neurogenesis, and the clinical presentation of Alzheimer's disease. Since the current understanding of the dynamics and homeostasis of the HSV-1 reservoir during latency is limited, the proposed model represents only a first step towards a complete understanding of the relationship between the copy number of HSV-1 during latency and Alzheimer's disease.
Identifiants
pubmed: 34635992
doi: 10.1007/s13365-021-01012-9
pii: 10.1007/s13365-021-01012-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
895-916Informations de copyright
© 2021. Journal of NeuroVirology, Inc.
Références
Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Lindsay RM (1995) A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 374(6521):450–453
pubmed: 7700353
Angka L, Khan ST, Kilgour MK, Xu R, Kennedy MA, Auer RC (2017) Dysfunctional natural killer cells in the aftermath of cancer surgery. Int J Mol Sci 18(8):1787
pmcid: 5578175
Arbizu J, Festari C, Altomare D, Walker Z, Bouwman F, Rivolta J, Nestor P (2018) Clinical utility of FDG-PET for the clinical diagnosis in MCI. Eur J Nucl Med Mol Imaging 45(9):1497–1508
pubmed: 29704037
Ariotti S, Hogenbirk MA, Dijkgraaf FE, Visser LL, Hoekstra ME, Song JY, Schumacher TN (2014) Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert. Science 346(6205):101–105
pubmed: 25278612
Aubert M, Chen Z, Lang R, Dang CH, Fowler C, Sloan DD, Jerome KR (2008) The antiapoptotic herpes simplex virus glycoprotein J localizes to multiple cellular organelles and induces reactive oxygen species formation. J Virol 82(2):617–629
pubmed: 17959661
Balu DT (2016) The NMDA receptor and schizophrenia: from pathophysiology to treatment. In Advances in Pharmacology Vol 76, pp 351–382 Academic Press
Bannert N, Avots A, Baier M, Serfling E, Kurth R (1999) GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes. Proc Natl Acad Sci 96(4):1541–1546
pubmed: 9990060
pmcid: 15509
Bzik DJ, Preston CM (1986) Analysis of DNA sequences which regulate the transcription of herpes simplex virus immediate early gene 3: DNA sequences required for enhancer-like activity and response to trans-activation by a virion polypeptide. Nucleic Acids Res 14(2):929–943
pubmed: 3003700
pmcid: 339474
Beghi E, Shorvon S (2011) Antiepileptic drugs and the immune system. Epilepsia 52:40–44
pubmed: 21542845
Bhattacharyya A, Chattopadhyay R, Hall EH, Mebrahtu ST, Ernst PB, Crowe SE (2010) Mechanism of hypoxia-inducible factor 1α-mediated Mcl1 regulation in Helicobacter pylori-infected human gastric epithelium. Am J Physiol Gastrointest Liver Physiol 299(5):G1177-G1186
Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Müller FJ, Loring JF, LaFerla FM (2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci 106(32):13594–13599
pubmed: 19633196
pmcid: 2715325
Bosetti F, Brizzi F, Barogi S, Mancuso M, Siciliano G, Tendi EA, Solaini G (2002) Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer’s disease. Neurobiol Aging 23(3):371–376
pubmed: 11959398
Briley D, Ghirardi V, Woltjer R, Renck A, Zolochevska O, Taglialatela G, Micci MA (2016) Preserved neurogenesis in non-demented individuals with AD neuropathology. Sci Rep 6(1):1–10
Brøchner AC, Mikkelsen S, Hegelund I, Hokland M, Mogensen O, Toft P (2016) The immune response is affected for at least three weeks after extensive surgery for ovarian cancer. Dan Med J 63(6):A5243
pubmed: 27264944
Bruni F, Polosa PL, Gadaleta MN, Cantatore P, Roberti M (2010) Nuclear respiratory factor 2 induces the expression of many but not all human proteins acting in mitochondrial DNA transcription and replication. J Biol Chem 285(6):3939–3948
pubmed: 19951946
Bush TS, St. Coeur M, Resendes KK, Rosmarin AG (2003) GA-binding protein (GABP) and Sp1 are required, along with retinoid receptors, to mediate retinoic acid responsiveness of CD18 (β2 leukocyte integrin): a novel mechanism of transcriptional regulation in myeloid cells. Blood, The Journal of the American Society of Hematology 101(1):311–317
Calaprice A (2000) The expanded quotable Einstein. Princeton University Press P 237
Camarena V, Kobayashi M, Kim JY, Roehm P, Perez R, Gardner J, Chao MV (2010) Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons. Cell Host Microbe 8(4):320–330
pubmed: 20951966
pmcid: 2988476
Campbell CT, Kolesar JE, Kaufman BA (2012) Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms 1819(9–10):921–929
Carpenter D, Hsiang C, Brown DJ, Jin L, Osorio N, BenMohamed L, Wechsler SL (2007) Stable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis. Virology 369(1):12–18
pubmed: 17727910
Castelo-Branco C, Soveral I (2014) The immune system and aging: a review. Gynecol Endocrinol 30(1):16–22
pubmed: 24219599
Chai YL, Xing H, Chong JR, Francis PT, Ballard CG, Chen CP, Lai MK (2018) Mitochondrial translocase of the outer membrane alterations may underlie dysfunctional oxidative phosphorylation in Alzheimer’s disease. J Alzheimers Dis 61(2):793–801
pubmed: 29254089
Chen JQ, Cammarata PR, Baines CP, Yager JD (2009) Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1793(10):1540–1570
Connor B, Young D, Yan Q, Faull RLM, Synek B, Dragunow M (1997) Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Mol Brain Res 49(1–2):71–81
pubmed: 9387865
Cosacak MI, Bhattarai P, Reinhardt S, Petzold A, Dahl A, Zhang Y, Kizil C (2019) Single-cell transcriptomics analyses of neural stem cell heterogeneity and contextual plasticity in a zebrafish brain model of amyloid toxicity. Cell Rep 27(4):1307–1318
pubmed: 31018142
Coskun PE, Beal MF, Wallace DC (2004) Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci 101(29):10726–10731
pubmed: 15247418
pmcid: 490002
De Chiara G, Marcocci ME, Civitelli L, Argnani R, Piacentini R, Ripoli C, Palamara AT (2010) APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells. PLoS One 5(11):e13989
Decker D, Tolba R, Springer W, Lauschke H, Hirner A, von Ruecker A (2005) Abdominal Surgical Interventions: Local and Systemic Consequences for the Immune System—a Prospective Study on Elective Gastrointestinal Surgery1. J Surg Res 126(1):12–18
pubmed: 15916969
Demars M, Hu YS, Gadadhar A, Lazarov O (2010) Impaired neurogenesis is an early event in the etiology of familial Alzheimer’s disease in transgenic mice. J Neurosci Res 88(10):2103–2117
pubmed: 20209626
pmcid: 3696038
Demars MP, Hollands C, Zhao KDT, Lazarov O (2013) Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation. Neurobiol Aging 34(10):2431–2440
pubmed: 23683827
pmcid: 3706568
Deshmane SL, Fraser NW (1989) During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure. J Virol 63(2):943–947
pubmed: 2536115
pmcid: 247770
Dewachter I, Filipkowski RK, Priller C, Ris L, Neyton J, Croes S, Godaux E (2009) Deregulation of NMDA-receptor function and down-stream signaling in APP [V717I] transgenic mice. Neurobiol Aging 30(2):241–256
pubmed: 17673336
Dhar SS, Wong-Riley MT (2009) Coupling of energy metabolism and synaptic transmission at the transcriptional level: role of nuclear respiratory factor 1 in regulating both cytochrome c oxidase and NMDA glutamate receptor subunit genes. J Neurosci 29(2):483–492
pubmed: 19144849
pmcid: 2775551
Diaz Brinton R, Ming Wang J (2006) Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer’s disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res 3(3):185–190
Doll JR, Hoebe K, Thompson RL, Sawtell NM (2020) Resolution of herpes simplex virus reactivation in vivo results in neuronal destruction. PLoS Pathogens 16(3):e1008296
Douville P, Hagmann M, Georgiev O, Schaffner W (1995) Positive and negative regulation at the herpes simplex virus ICP4 and ICPO TAATGARAT motifs. Virology 207(1):107–116
pubmed: 7871718
Du T, Zhou G, Roizman B (2013) Modulation of reactivation of latent herpes simplex virus 1 in ganglionic organ cultures by p300/CBP and STAT3. Proc Natl Acad Sci 110(28):E2621–E2628
pubmed: 23788661
pmcid: 3710862
El Gaamouch F, Buisson A, Moustié O, Lemieux M, Labrecque S, Bontempi B, Nicole O (2012) Interaction between αCaMKII and GluN2B controls ERK-dependent plasticity. J Neurosci 32(31):10767–10779
pubmed: 22855824
pmcid: 6621385
Feldman LT, Ellison AR, Voytek CC, Yang L, Krause P, Margolis TP (2002) Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Proc Natl Acad Sci U S A 99(2):978–983
pubmed: 11773630
pmcid: 117416
Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kyin M, Sisodia SS (2001) Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 32(5):911–926
pubmed: 11738035
Fountoulakis NK (2012) The possible involvement of NMDA glutamate receptor in the etiopathogenesis of bipolar disorder. Curr Pharm Des 18(12):1605–1608
pubmed: 22280433
Fumagalli F, Racagni G, Riva MA (2006) The expanding role of BDNF: a therapeutic target for Alzheimer’s disease?. Pharmacogenomics J 6(1):8–15
pubmed: 16314887
Gatt A, Lee H, Williams G, Thuret S, Ballard C (2019) Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis. Neurobiol Aging 76:166–180
pubmed: 30716542
Garzon DJ, Fahnestock M (2007) Oligomeric amyloid decreases basal levels of brain-derived neurotrophic factor (BDNF) mRNA via specific downregulation of BDNF transcripts IV and V in differentiated human neuroblastoma cells. J Neurosci 27(10):2628–2635
pubmed: 17344400
pmcid: 6672502
Ghiringhelli F, Apetoh L (2014) The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy. Expert Rev Clin Immunol 10(1):19–30
pubmed: 24308838
Gugneja S, Virbasius CM, Scarpulla RC (1996) Nuclear respiratory factors 1 and 2 utilize similar glutamine-containing clusters of hydrophobic residues to activate transcription. Mol Cell Biol 16(10):5708–5716
pubmed: 8816484
pmcid: 231571
Hagmann M, Georgiev O, Schaffner W, Douville P (1995) Transcription factors interacting with herpes simplex virus α gene promoters in sensory neurons. Nucleic Acids Res 23(24):4978–4985
pubmed: 8559654
pmcid: 307502
Harbauer AB, Zahedi RP, Sickmann A, Pfanner N, Meisinger C (2014) The protein import machinery of mitochondria—a regulatory hub in metabolism, stress, and disease. Cell Metab 19(3):357–372
pubmed: 24561263
Harris SA, Harris EA (2018) Molecular mechanisms for herpes simplex virus type 1 pathogenesis in Alzheimer’s disease. Front Aging Neurosci 10:48
pubmed: 29559905
pmcid: 5845560
Held K, Derfuss T (2011) Control of HSV-1 latency in human trigeminal ganglia—current overview. J Neurovirol 17(6):518–527
pubmed: 22139603
Henderson G, Peng W, Jin L, Perng GC, Nesburn AB, Wechsler SL, Jones C (2002) Regulation of caspase 8–and caspase 9–induced apoptosis by the herpes simplex virus type 1 latency-associated transcript. Neurovirol 8
Henken DB, Goldstein ME, Martin JR (1993) Herpes simplex virus type-2 infection by a footpad route results in neuronal death in mouse spinal ganglia. J Neurol Sci 115(2):177–183
pubmed: 8387099
Herrera FJ, Triezenberg SJ (2004) VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. J Virol 78(18):9689–9696
pubmed: 15331701
pmcid: 515004
Hill JM, Ball MJ, Neumann DM, Azcuy AM, Bhattacharjee PS, Bouhanik S, Kaufman HE (2008) The high prevalence of herpes simplex virus type 1 DNA in human trigeminal ganglia is not a function of age or gender. J Virol 82(16):8230–8234
pubmed: 18550674
pmcid: 2519549
Hill JM, Garza H, Helmy MF, Cook SD, Osborne PA, Johnson M, Gebhardt BM (1997) Nerve growth factor antibody stimulates reactivation of ocular herpes simplex virus type 1 in latently infected rabbits. J Neurovirol 3(3):206–211
pubmed: 9200068
Hock C, Heese K, Hulette C, Rosenberg C, Otten U (2000) Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 57(6):846–851
pubmed: 10867782
Hung SY, Huang WP, Liou HC, Fu WM (2009) Autophagy protects neuron from Aβ-induced cytotoxicity. Autophagy 5(4):502–510
pubmed: 19270530
Hyman BT, Damasio H, Damasio AR, Van Hoesen GW (1989) Alzheimer’s disease. Annu Rev Public Health 10(115–140)
Hynd MR, Scott HL, Dodd PR (2004) Differential expression of N-methyl-D-aspartate receptor NR2 isoforms in Alzheimer’s disease. J Neurochem 90(4):913–919
pubmed: 15287897
Inczedy-Farkas G, Trampush JW, Perczel Forintos D, Beech D, Andrejkovics M, Varga Z, Molnar MJ (2014) Mitochondrial DNA mutations and cognition: a case-series report. Arch Clin Neuropsychol 29(4):315–321
pubmed: 24777554
Ishii K, Kitagaki H, Kono M, Mori E (1996) Decreased medial temporal oxygen metabolism in Alzheimer’s disease shown by PET. J Nucl Med 37(7):1159
pubmed: 8965188
Itabashi S, Arai H, Matsui T, Higuchi S, Sasaki H (1997) Herpes simplex virus and risk of Alzheimer’s disease. The Lancet 349(9058):1102
Itzhaki RF, Lathe R, Balin BJ, Ball MJ, Bearer EL, Braak H, Del Tredici K (2016) Microbes and Alzheimer’s disease. Journal of Alzheimer’s Disease: JAD 51(4):979
pubmed: 26967229
Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA (1997) Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. The Lancet 349(9047):241–244
Jamieson GA, Maitland NJ, Wilcock GK, Craske J, Itzhaki RF (1991) Latent herpes simplex virus type 1 in normal and Alzheimer’s disease brains. J Med Virol 33(4):224–227
pubmed: 1649907
Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Savonenko AV (2005) Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease. J Neurosci 25(21):5217–5224
pubmed: 15917461
pmcid: 4440804
Jerome KR, Chen Z, Lang R, Torres MR, Hofmeister J, Smith S, Corey L (2001) HSV and glycoprotein J inhibit caspase activation and apoptosis induced by granzyme B or Fas. J Immunol 167(7):3928–3935
pubmed: 11564811
Jin L, Peng W, Perng GC, Brick DJ, Nesburn AB, Jones C, Wechsler SL (2003) Identification of herpes simplex virus type 1 latency-associated transcript sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype. J Virol 77(11):6556–6561
pubmed: 12743314
pmcid: 155006
Kamei N, Tanaka N, Oishi Y, Hamasaki T, Nakanishi K, Sakai N, Ochi M (2007) BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote corticospinal axon growth in organotypic cocultures. Spine 32(12):1272–1278
pubmed: 17515814
Keller JN, Pang Z, Geddes JW, Begley JG, Germeyer A, Waeg G, Mattson MP (1997) Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid β-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J Neurochem 69(1):273–284
pubmed: 9202320
Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18(4):357–368
pubmed: 15004004
Knickelbein JE, Khanna KM, Yee MB, Baty CJ, Kinchington PR, Hendricks RL (2008) Noncytotoxic lytic granule–mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 322(5899):268–271
pubmed: 18845757
pmcid: 2680315
Knipe DM, Cliffe A (2008) Chromatin control of herpes simplex virus lytic and latent infection. Nat Rev Microbiol 6(3):211–221
pubmed: 18264117
Kobayashi M, Wilson AC, Chao MV, Mohr I (2012) Control of viral latency in neurons by axonal mTOR signaling and the 4E-BP translation repressor. Genes Dev 26(14):1527–1532
pubmed: 22802527
pmcid: 3404381
Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci 92(19):8856–8860
pubmed: 7568031
pmcid: 41066
Kramer MF, Coen DM (1995) Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia latently infected with herpes simplex virus. J Virol 69(3):1389–1399
pubmed: 7853471
pmcid: 188725
Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Lombroso PJ (2010) Aβ-mediated NMDA receptor endocytosis in Alzheimer’s disease involves ubiquitination of the tyrosine phosphatase STEP61. J Neurosci 30(17):5948–5957
pubmed: 20427654
pmcid: 2868326
Kwiatkowski DL, Thompson HW, Bloom DC (2009) The polycomb group protein Bmi1 binds to the herpes simplex virus 1 latent genome and maintains repressive histone marks during latency. J Virol 83(16):8173–8181
pubmed: 19515780
pmcid: 2715759
Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Klein WL (2007) Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J Neurosci 27(4):796–807
pubmed: 17251419
pmcid: 6672917
Lajoie I, Nugent S, Debacker C, Dyson K, Tancredi FB, Badhwar A, Bocti C (2017) Application of calibrated fMRI in Alzheimer's disease. NeuroImage: Clinical 15:348–358
Lakhan SE, Caro M, Hadzimichalis N (2013) NMDA receptor activity in neuropsychiatric disorders. Front Psych 4:52
LaMarco K, Thompson CC, Byers BP, Walton EM, McKnight SL (1991) Identification of Ets-and notch-related subunits in GA binding protein. Science 253(5021):789–792
pubmed: 1876836
LaMarco KL, McKnight SL (1989) Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes. Genes Dev 3(9):1372–1383
pubmed: 2558055
Lalonde R, Kim HD, Maxwell JA, Fukuchi K (2005) Exploratory activity and spatial learning in 12-month-old APP695SWE/co+ PS1/ΔE9 mice with amyloid plaques. Neurosci Lett 390(2):87–92
pubmed: 16169151
La Rosa F, Agostini S, Bianchi A, Nemni R, Piancone F, Marventano I, Clerici M (2019) Herpes simplex virus-1 (HSV-1) infection induces a potent but ineffective IFN-λ production in immune cells of AD and PD patients. J Transl Med 17(1):286
pubmed: 31455413
pmcid: 6712644
La Rosa F, Saresella M, Baglio F, Piancone F, Marventano I, Calabrese E, Clerici M (2017) Immune and imaging correlates of mild cognitive impairment conversion to Alzheimer’s disease. Sci Rep 7(1):1–10
La Rosa F, Saresella M, Piancone F, Marventano I, Calabrese E, Nemni R, Clerici M (2016) P1–157: Increased TLR8 and 9 expression correlates with preserved hyppocampal volumes and lack of progression to Alzheimer’s disease in individuals with a diagnosis of mild cognitive impairment. Alzheimers Dement 12:P463–P463
Lathe R, Haas JG (2017) Distribution of cellular HSV-1 receptor expression in human brain. J Neurovirol 23(3):376–384
pubmed: 27981441
Lazarov O, Hollands C (2016) Hippocampal neurogenesis: learning to remember. Prog Neurobiol 138:1–18
pubmed: 26855369
Lee CW, Ferreon JC, Ferreon ACM, Arai M, Wright PE (2010) Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation. Proc Natl Acad Sci 107(45):19290–19295
pubmed: 20962272
pmcid: 2984141
Leger AJS, Hendricks RL (2011) CD8+ T cells patrol HSV-1-infected trigeminal ganglia and prevent viral reactivation. J Neurovirol 17(6):528–534
Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, Dartigues JF (2008) Seropositivity to herpes simplex virus antibodies and risk of Alzheimer’s disease: a population-based cohort study. PLoS One 3(11):e3637
Li Puma DD, Piacentini R, Leone L, Gironi K, Marcocci ME, De Chiara G, Grassi C (2019) Herpes simplex virus type-1 infection impairs adult hippocampal neurogenesis via amyloid-β protein accumulation. Stem Cells 37(11):1467–1480
pubmed: 31381841
Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A, Kukull W (2008) Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci 105(11):4441–4446
pubmed: 18332434
pmcid: 2393743
Lin WR, Graham J, MacGowan SM, Wilcock GK, Itzhaki RF (1998) Alzheimer's disease, herpes virus in brain, apolipoprotein E4 and herpes labialis. Alzheimers Reports 1(3)
Liu C, Dai SK, Sun Z, Wang Z, Liu PP, Du HZ, Teng ZQ (2019) GA-binding protein GABPβ1 is required for the proliferation of neural stem/progenitor cells. Stem Cell Res 39:101501
Loopuijt LD, Schmidt WJ (1998) The role of NMDA receptors in the slow neuronal degeneration of Parkinson’s disease. Amino Acids 14(1–3):17–23
pubmed: 9871436
Lu J, Zuo L, Du S, Liu L (2016) The oncogenicity of Epstein-Barr virus: being more or less is to be concerned. Cancer Cell & Microenvironment 3
Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of Aβ accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437–1449
pubmed: 16551656
Manczak M, Park BS, Jung Y, Reddy PH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer’s disease. NeuroMol Med 5(2):147–162
Marcello E, Gardoni F, Mauceri D, Romorini S, Jeromin A, Epis R, Di Luca M (2007) Synapse-associated protein-97 mediates α-secretase ADAM10 trafficking and promotes its activity. J Neurosci 27(7):1682–1691
pubmed: 17301176
pmcid: 6673742
Mark KE, Wald A, Magaret AS, Selke S, Olin L, Huang ML, Corey L (2008) Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis 198(8):1141–1149
pubmed: 18783315
Mastroeni D, Khdour OM, Delvaux E, Nolz J, Olsen G, Berchtold N, Coleman PD (2017) Nuclear but not mitochondrial-encoded oxidative phosphorylation genes are altered in aging, mild cognitive impairment, and Alzheimer’s disease. Alzheimers Dement 13(5):510–519
pubmed: 27793643
Maurer I, Zierz S, Möller HJ (2000) A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol Aging 21(3):455–462
pubmed: 10858595
McBain CJ, Mayer ML (1994) N-methyl-D-aspartic acid receptor structure and function. Physiol Rev 74(3):723–760
pubmed: 8036251
McLean JH, Shipley MT, Bernstein DI, Corbett D (1993) Selective lesions of neural pathways following viral inoculation of the olfactory bulb. Exp Neurol 122(2):209–222
pubmed: 8104818
Melroe GT, Silva L, Schaffer PA, Knipe DM (2007) Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: potential role in blocking IFN-β induction. Virology 360(2):305–321
pubmed: 17126870
Miller CS, Danaher RJ, Jacob RJ (1998) Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence. Crit Rev Oral Biol Med 9(4):541–562
pubmed: 9825226
Mishizen-Eberz AJ, Rissman RA, Carter TL, Ikonomovic MD, Wolfe BB, Armstrong DM (2004) Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer’s disease pathology. Neurobiol Dis 15(1):80–92
pubmed: 14751773
Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, Rábano A, Cafini F, Pallas-Bazarra N, Llorens-Martín M (2019) Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med 25(4):554–560
pubmed: 30911133
Mori I, Nishiyama Y, Yokochi T, Kimura Y (2005) Olfactory transmission of neurotropic viruses. J Neurovirol 11(2):129–137
pubmed: 16036791
Murray KD, Gall CM, Jones EG, Isackson PJ (1994) Differential regulation of brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase messenger RNA expression in Alzheimer’s disease. Neuroscience 60(1):37–48
pubmed: 8052419
Nair B, Wong-Riley MT (2016) Transcriptional regulation of brain-derived neurotrophic factor coding exon ix role of nuclear respiratory factor 2. J Biol Chem 291(43):22583–22593
pubmed: 27624937
pmcid: 5077195
Narayanan A, Nogueira ML, Ruyechan WT, Kristie TM (2005) Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1. J Biol Chem 280(2):1369–1375
pubmed: 15522876
Nguyen ML, Blaho JA (2006) Apoptosis during herpes simplex virus infection. Adv Virus Res 69:67–97
Nogueira ML, Wang VE, Tantin D, Sharp PA, Kristie TM (2004) Herpes simplex virus infections are arrested in Oct-1-deficient cells. Proc Natl Acad Sci 101(6):1473–1478
pubmed: 14745036
pmcid: 341744
Nunomura A, Tamaoki T, Motohashi N, Nakamura M, McKeel DW Jr, Tabaton M, Zhu X (2012) The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. J Neuropathol Exp Neurol 71(3):233–241
pubmed: 22318126
Oka S, Leon J, Sakumi K, Ide T, Kang D, LaFerla FM, Nakabeppu Y (2016) Human mitochondrial transcriptional factor A breaks the mitochondria-mediated vicious cycle in Alzheimer’s disease. Sci Rep 6:37889
pubmed: 27897204
pmcid: 5126576
Olney JW, Tenkova T, Dikranian K, Muglia LJ, Jermakowicz WJ, D’Sa C, Roth KA (2002) Ethanol-induced caspase-3 activation in the in vivo developing mouse brain. Neurobiol Dis 9(2):205–219
Olofsdotter K, Lindvall O, Asztely F (2000) Increased synaptic inhibition in dentate gyrus of mice with reduced levels of end
Ongwijitwat S, Liang HL, Graboyes EM, Wong-Riley MT (2006) Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs. Gene 374:39–49
pubmed: 16516409
Pandey JP, Olsson J, Weidung B, Kothera RT, Johansson A, Eriksson S, Lövheim H (2020) An Ig γ Marker Genotype Is a Strong Risk Factor for Alzheimer Disease, Independent of Apolipoprotein E ε4 Genotype. J Immunol 205(5):1318–1322
pubmed: 32709662
Papadimitriou C, Celikkaya H, Cosacak MI, Mashkaryan V, Bray L, Bhattarai P, Antos CL (2018) 3D culture method for Alzheimer’s disease modeling reveals interleukin-4 rescues Aβ42-induced loss of human neural stem cell plasticity. Dev Cell 46(1):85–101
pubmed: 29974866
Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14(1):7–23
pubmed: 23254191
Parker WD, Parks JK (1995) Cytochrome c oxidase in Alzheimer’s disease brain: purification and characterization. Neurology 45(3):482–486
pubmed: 7898701
Patterson SL, Abel T, Deuel TA, Martin KC, Rose JC, Kandel ER (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16(6):1137–1145
pubmed: 8663990
Pedrós I, Petrov D, Allgaier M, Sureda F, Barroso E, Beas-Zarate C, Folch J (2014) Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse model of Alzheimer's disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1842(9):1556–1566
Peng W, Jin L, Henderson G, Perng GC, Brick DJ, Nesburn AB, Jones C (2004) Mapping herpes simplex virus type 1 latency-associated transcript sequences that protect from apoptosis mediated by a plasmid expressing caspase-8. J Neurovirol 10(4):260–265
pubmed: 15371157
Perng GC, Ghiasi H, Slanina SM, Nesburn AB, Wechsler SL (1996) The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1.5 kilobases of the 8.3-kilobase primary transcript. J Virol 70(2):976–984
Petrov D, Luque M, Pedrós I, Ettcheto M, Abad S, Pallàs M, Camins A (2016) Evaluation of the role of JNK1 in the hippocampus in an experimental model of familial Alzheimer’s disease. Mol Neurobiol 53(9):6183–6193
pubmed: 26558630
Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Wyss-Coray T (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Investig 118(6):2190–2199
pubmed: 18497889
pmcid: 2391284
Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 7(5):695–702
pubmed: 1742020
Polansky H (2003) Microcompetition with foreign DNA and the origin of chronic disease. Center for the Biology of Chronic.
Polansky H, Schwab H (2018a) Copy number of latent viruses, oncogenicity, and the microcompetition model. Oncotarget 9(60):31568
pubmed: 30167078
pmcid: 6114963
Polansky H, Schwab H (2018b) How a disruption of the competition between HIF-1 and p53 for limiting p300/CBP by latent viruses can cause disease. Genes Cancer 9(5–6):153
pubmed: 30603052
pmcid: 6305108
Polansky H, Schwab H (2019) How latent viruses cause breast cancer: an explanation based on the microcompetition model. Bosn J Basic Med Sci 19(3):221
pubmed: 30579323
pmcid: 6716096
Preston CM, Efstathiou S (2007) Molecular basis of HSV latency and reactivation. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K, editors. Human herpesviruses: biology, therapy, and immunoprophylaxis. United Kingdom: Cambridge University Press Chapter 33
Priya A, Johar K, Wong-Riley MT (2013) Nuclear respiratory factor 2 regulates the expression of the same NMDA receptor subunit genes as NRF-1: both factors act by a concurrent and parallel mechanism to couple energy metabolism and synaptic transmission. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1833(1):48–58
Polansky H, Javaherian A (2015a) Microcompetition with latent Epstein-Barr virus causes a transcription factor deficiency, under-expression of retinoblastoma, and classic Hodgkin lymphoma. Int J Res Med Sci 3(6):1562
Polansky H, Javaherian A (2015b) Latent viruses, microcompetition, transcription factor deficiency and the cause of acute lymphoblastic leukemia. J Adv Med 541–543
Piacentini R, Civitelli L, Ripoli C, Marcocci ME, De Chiara G, Garaci E, Grassi C (2011) HSV-1 promotes Ca2+-mediated APP phosphorylation and Aβ accumulation in rat cortical neurons. Neurobiol Aging 32(12):2323-e13
pubmed: 20674092
Piacentini R, Puma DDL, Ripoli C, Marcocci ME, De Chiara G, Garaci E, Grassi C (2015) Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-β protein accumulation. Sci Rep 5(1):1–14
Rice AC, Keeney PM, Algarzae NK, Ladd AC, Thomas RR, Bennett JP Jr (2014) Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer’s disease hippocampi. J Alzheimers Dis 40(2):319–330
pubmed: 24448779
Richards BA, Frankland PW (2017) The persistence and transience of memory. Neuron 94(6):1071–1084
pubmed: 28641107
Røge R, Møller BK, Andersen CR, Correll CU, Nielsen J (2012) Immunomodulatory effects of clozapine and their clinical implications: what have we learned so far?. Schizophr Res 140(1–3):204–213
pubmed: 22831769
Rosmarin AG, Resendes KK, Yang Z, McMillan JN, Fleming SL (2004) GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein–protein interactions. Blood Cells Mol Dis 32(1):143–154
pubmed: 14757430
Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, Hiltunen M (2013) Impaired autophagy and APP processing in Alzheimer’s disease: the potential role of Beclin 1 interactome. Prog Neurobiol 106:33–54
pubmed: 23827971
Sawtell NM (1997) Comprehensive quantification of herpes simplex virus latency at the single-cell level. J Virol 71(7):5423–5431
pubmed: 9188614
pmcid: 191782
Sawtell NM, Poon DK, Tansky CS, Thompson RL (1998) The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. J Virol 72(7):5343–5350
pubmed: 9620987
pmcid: 110155
Sharrocks AD (2001) The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2(11):827–837
pubmed: 11715049
Shen JH, Huang KYA, Chao-Yu C, Chen CJ, Lin TY, Huang YC (2015) Seroprevalence of herpes simplex virus type 1 and 2 in Taiwan and risk factor analysis, 2007. PLoS One 10(8):e0134178
pubmed: 26252011
pmcid: 4529201
Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, Zhu X (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120(3):419–429
pubmed: 22077634
Shieh PB, Hu SC, Bobb K, Timmusk T, Ghosh A (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20(4):727–740
pubmed: 9581764
Singh N, Tscharke DC (2020) Herpes simplex virus latency is noisier the closer we look. J Virol 94(4)
Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Greengard P (2005) Regulation of NMDA receptor trafficking by amyloid-β. Nat Neurosci 8(8):1051–1058
pubmed: 16025111
Sörensen A, Blazhenets G, Rücker G, Schiller F, Meyer PT, Frings L, Alzheimer's Disease Neuroimaging Initiative (2019) Prognosis of conversion of mild cognitive impairment to Alzheimer's dementia by voxel-wise Cox regression based on FDG PET data. NeuroImage: Clinical 21:101637
Suzuki WA, Zola-Morgan S, Squire LR, Amaral DG (1993) Lesions of the perirhinal and parahippocampal cortices in the monkey produce long-lasting memory impairment in the visual and tactual modalities. J Neurosci 13(6):2430–2451
pubmed: 8501516
pmcid: 6576496
Swaminathan G, Zhu W, Plowey ED (2016) BECN1/Beclin 1 sorts cell-surface APP/amyloid β precursor protein for lysosomal degradation. Autophagy 12(12):2404–2419
pubmed: 27715386
pmcid: 5173276
Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ (2001) N-Methyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer’s disease. J Neurol Sci 182(2):151–159
pubmed: 11137521
Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Tsien JZ (1999) Genetic enhancement of learning and memory in mice. Nature 401(6748):63–69
pubmed: 10485705
Taus NS, Mitchell WJ (2001) The transgenic ICP4 promoter is activated in Schwann cells in trigeminal ganglia of mice latently infected with herpes simplex virus type 1. J Virol 75(21):10401–10408
pubmed: 11581408
pmcid: 114614
Thompson RL, Sawtell NM (1997) The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. J Virol 71(7):5432–5440
pubmed: 9188615
pmcid: 191783
Tobin MK, Musaraca K, Disouky A, Shetti A, Bheri A, Honer WG, Lazarov O (2019) Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell 24(6):974–982
pubmed: 31130513
pmcid: 6608595
Tohgi H, Yonezawa H, Takahashi S, Sato N, Kato E, Kudo M, Sasaki T (1998) Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer’s type and vascular dementia with deep white matter changes. Neuroradiology 40(3):131–137
pubmed: 9561514
Tong L, Thornton PL, Balazs R, Cotman CW (2001) β-amyloid-(1–42) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival is not compromised. J Biol Chem 276(20):17301–17306
pubmed: 11278679
Triezenberg SJ, LaMarco KL, McKnight SL (1988) Evidence of DNA: protein interactions that mediate HSV-1 immediate early gene activation by VP16. Genes Dev 2(6):730–742
pubmed: 2843426
Tzeng NS, Chung CH, Lin FH, Chiang CP, Yeh CB, Huang SY, Chiang WS (2018) Anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections—a nationwide, population-based cohort study in Taiwan. Neurotherapeutics 15(2):417–429
pubmed: 29488144
pmcid: 5935641
Ueda A, Akagi T, Yokota T (2017) GA-binding protein alpha is involved in the survival of mouse embryonic stem cells. Stem Cells 35(11):2229–2238
pubmed: 28762569
Ułas J, Cotman CW (1997) Decreased expression of N-methyl-D-aspartate receptor 1 messenger RNA in select regions of Alzheimer brain. Neuroscience 79(4):973–982
pubmed: 9219960
Venkitaramani DV, Moura PJ, Picciotto MR, Lombroso PJ (2011) Striatal-enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. Eur J Neurosci 33(12):2288–2298
pubmed: 21501258
pmcid: 3118976
Verges DK, Restivo JL, Goebel WD, Holtzman DM, Cirrito JR (2011) Opposing synaptic regulation of amyloid-β metabolism by NMDA receptors in vivo. J Neurosci 31(31):11328–11337
pubmed: 21813692
pmcid: 3329800
Vitlic A, Lord JM, Phillips AC (2014) Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system. Age 36(3):9631
pubmed: 24562499
pmcid: 4082590
Vogel JL, Kristie TM (2000) The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP. EMBO J 19(4):683–690
pubmed: 10675337
pmcid: 305606
Wang R, Dineley KT, Sweatt JD, Zheng H (2004) Presenilin 1 familial Alzheimer’s disease mutation leads to defective associative learning and impaired adult neurogenesis. Neuroscience 126(2):305–312
pubmed: 15207348
Wang T, Lao U, Edgar BA (2009) TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J Cell Biol 186(5):703–711
pubmed: 19720874
pmcid: 2742187
Wang W, Zhao F, Ma X, Perry G, Zhu X (2020) Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegener 15:1–22
Wiedemann N, Pfanner N (2017) Mitochondrial machineries for protein import and assembly. Annu Rev Biochem 86:685–714
pubmed: 28301740
World Health Organization (2018) Herpes simplex virus. http://www.who.int/en/news-room/fact-sheets/detail/herpes-simplex-virus . Published 2018. Accessed 27 Aug 2018
Wozniak MA, Mee AP, Itzhaki RF (2009) Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland 217(1):131–138
Xu S, Zhong M, Zhang L, Wang Y, Zhou Z, Hao Y, Yu Z (2009) Overexpression of Tfam protects mitochondria against β-amyloid-induced oxidative damage in SH-SY5Y cells. FEBS J 276(14):3800–3809
pubmed: 19496804
Yang L, Voytek CC, Margolis TP (2000) Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1. J Virol 74(1):209–217
pubmed: 10590108
pmcid: 111530
Yang ZF, Drumea K, Mott S, Wang J, Rosmarin AG (2014) GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis. Mol Cell Biol 34(17):3194–3201
pubmed: 24958105
pmcid: 4135556
You Y, Cheng AC, Wang MS, Jia RY, Sun KF, Yang Q, Zhao XX (2017) The suppression of apoptosis by α-herpesvirus. Cell Death Dis 8(4):e2749–e2749
pubmed: 28406478
pmcid: 5477576
Young-Collier KJ, McArdle M, Bennett JP (2012) The dying of the light: mitochondrial failure in Alzheimer’s disease. J Alzheimers Dis 28(4):771–781
pubmed: 22057028
Yu S, Cui K, Jothi R, Zhao DM, Jing X, Zhao K, Xue HH (2011) GABP controls a critical transcription regulatory module that is essential for maintenance and differentiation of hematopoietic stem/progenitor cells. Blood, The Journal of the American Society of Hematology 117(7):2166–2178
Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Lombroso PJ (2010) Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proc Natl Acad Sci 107(44):19014–19019
pubmed: 20956308
pmcid: 2973892
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132(4):645–660
pubmed: 18295581
Zheng F, Zhou X, Moon C, Wang H (2012) Regulation of brain-derived neurotrophic factor expression in neurons. International Journal of Physiology, Pathophysiology and Pharmacology 4(4):188
pubmed: 23320132
pmcid: 3544221
Zhou CH, Zhang XP, Liu F, Wang W (2015) Modeling the interplay between the HIF-1 and p53 pathways in hypoxia. Sci Rep 5:13834
pubmed: 26346319
pmcid: 4561886
Zhu W, Swaminathan G, Plowey ED (2014) GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes. Autophagy 10(9):1622–1636
pubmed: 25046113
pmcid: 4206539
Zuo L, Yu H, Liu L, Tang Y, Wu H, Yang J, Li G (2015) The copy number of Epstein-Barr virus latent genome correlates with the oncogenicity by the activation level of LMP1 and NF-κB. Oncotarget 6(38):41033
pubmed: 26517512
pmcid: 4747387