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How microcompetition with latent viruses can cause α synuclein aggregation, mitochondrial dysfunction, and eventually Parkinson’s disease

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Abstract

The cause of most Parkinson’s disease cases is unknown. However, it is well documented that mitochondrial dysfunction and misfolded α synuclein aggregation are important cellular abnormalities associated with the disease. In this paper, we use the microcompetition model to show how latent viruses, which infect the central and peripheral nervous systems, can cause the observed mitochondrial dysfunction and excess α synuclein aggregation, and eventually, Parkinson’s disease.

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References

  • Ahting U, Floss T, Uez N, Schneider-Lohmar I, Becker L, Kling E, Iuso A, Bender A, de Angelis MH, Gailus-Durner V, Fuchs H, Meitinger T, Wurst W, Prokisch H, Klopstock T (2009) Neurological phenotype and reduced lifespan in heterozygous Tim23 knockout mice, the first mouse model of defective mitochondrial import. BBA-Bioenergetics 1787(5):371–376

    Article  CAS  Google Scholar 

  • Bednar MM, Sturdevant CB, Tompkins LA, et al (2015) Compartmentalization, viral evolution, and viral latency of HIV in the CNS. Curr HIV/AIDS Rep. 12(2):262

  • Błaszczyk JW (2018) The emerging role of energy metabolism and neuroprotective strategies in Parkinson’s disease. Front Aging Neurosci 10:301

    Article  Google Scholar 

  • Blesa JR, Prieto-Ruiz JA, Hernández JM, Hernández-Yago J (2007) NRF-2 transcription factor is required for human TOMM20 gene expression. Gene 391(1–2):198–208

    Article  CAS  Google Scholar 

  • Brundin P, Melki R (2017) Prying into the prion hypothesis for Parkinson’s disease. The Journal of Neuroscience 37(41):9808–9818

    Article  CAS  Google Scholar 

  • Calaprice A (2000) The Expande Quotable Einstein. Princeton University Press P. 237

  • Chen C, Turnbull D, Reeve A (2019) Mitochondrial dysfunction in Parkinson’s disease—cause or consequence? Biology (Basel) 8(2):38

    CAS  Google Scholar 

  • Decressac M, Mattsson B, Weikop P, Lundblad M, Jakobsson J, Björklund A (2013) TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity. PNAS 110(19):E1817–E1826

    Article  CAS  Google Scholar 

  • Demishtein-Zohary K, Azem A (2016) The TIM23 mitochondrial protein import complex: function and dysfunction. Cell Tissue Res 367(1):33–41

    Article  Google Scholar 

  • Esteves AR, Arduíno DM, Silva DF, Oliveira CR, Cardoso SM (2011) Mitochondrial dysfunction: the road to alpha-synuclein oligomerization in PD. Parkinsons Dis 2011:693761

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franco-Iborra S, Cuadros T, Parent A, Romero-Gimenez J, Vila M, Perier C (2018) Defective mitochondrial protein import contributes to complex I-induced mitochondrial dysfunction and neurodegeneration in Parkinson’s disease. Cell Death and Disease 9(11):1122

    Article  Google Scholar 

  • Ganjam G, Bolte K, Matschke L, Neitemeier S, Dolga A, Höllerhage M, Höglinger G, Adamczyk A, Decher N, Oertel W, Culmsee C (2019) Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neurons. Cell Death and Disease 10(11):865

    Article  CAS  Google Scholar 

  • Grinde B (2013) Herpesviruses: latency and reactivation – viral strategies and host response. J Oral Microbiol 23:56

    Google Scholar 

  • Grünewald A, Kumar KR, Sue CM (2019) New insights into the complex role of mitochondria in Parkinson’s disease. Prog Neurobiol 177:73

  • Hegarty, Shane & O Leary, Eimear & Solger, Franziska & Stanicka, Joanna & Sullivan, Aideen & O’Keeffe, Gerard. (2016). A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease. Neurotox Res

  • Janknecht R (2002) The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease. Histol Histopathol 17:657–668

    CAS  PubMed  Google Scholar 

  • Johnson ME, Stecher B, Labrie V, Brundin L, Brundin P (2019) Triggers, facilitators, and aggravators: Redefining Parkinson’s disease pathogenesis. Trends Neurosci 42(1):4

  • Kulawiak B, Höpker J, Gebert M, Guiard B, Wiedemann N, Gebert N (2013) The mitochondrial protein import machinery has multiple connections to the respiratory chain. Biochimica et Biophysica Acta (BBA) – Bioenergetics 1827(5): 612–616

  • Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132(1):27

    Article  CAS  Google Scholar 

  • Limphaibool N, Iwanowski P, Holstad M, Kobylarek D and Kozubski WH (2019) Infectious etiologies of Parkinsonism: pathomechanisms and clinical implications. Front neurol 10:652

  • Lopes da Fonseca T, Villar-Piqué A, Outeiro TF (2015) The Interplay between alpha-synuclein clearance and spreading. Biomolecules 5(2):435

  • Lautenschläger J, Wagner-Valladolid S, Stephens AD, et al (2020) Intramitochondrial proteostasis is directly coupled to α-synuclein and amyloid β 1–42 pathologies [published online ahead of print, 2020 May 8]. J Biol Chem

  • Menon MB, Dhamija S (2018) Beclin 1 phosphorylation—at the Center of Autophagy Regulation. Front Cell Dev Biol 6:137

    Article  Google Scholar 

  • Metcalf DJ, García-Arencibia M, Hochfeld WE, Rubinsztein DC (2012) Autophagy and misfolded proteins in neurodegeneration. Exp Neurol 238(1):22–28

    Article  CAS  Google Scholar 

  • Moreno-Gonzalez I, Soto C (2011) Misfolded protein aggregates: mechanisms, structures and potential for disease transmission. Semin Cell Dev Biol 22(5):482

    Article  CAS  Google Scholar 

  • Olsen L, Dowd E, McKernan D (2018) A role for viral infections in Parkinson’s etiology? Neuronal Signal 2(2)

  • Polansky H (2003) Microcompetition with foreign DNA and the origin of chronic disease. The Center for the Biology of Chronic Disease, New York

    Google Scholar 

  • Polansky H, Javaherian A (2015) The latent cytomegalovirus decreases telomere length by microcompetition. Open Med (Wars) 10(1):294–296

    CAS  Google Scholar 

  • Polansky H, Schwab H (2018) Copy number of latent viruses, oncogenicity, and the microcompetition model. Oncotarget 9(60):31568–31569

  • Polansky H, Schwab H (2018) How a disruption of the Competition between HIF-1 and p53 for limiting p300/CBP by Latent Viruses Can Cause Disease. Genes Cancer

  • 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):221–226

    CAS  PubMed  PubMed Central  Google Scholar 

  • Popis M (2019) Dysfunction of mitochondria as the basis of Parkinson’s disease. Medical Journal of Cell Biology 6(4):174–181

    Article  Google Scholar 

  • Prieto-Ruiz JA, Alis R, García-Benlloch S, Sáez-Atiénzar S, Ventura I, Hernández-Andreu JM, Blesa JR (2018) Expression of the human TIMM23 and TIMM23B genes is regulated by the GABP transcription factor. BBA - Gene Regulatory Mechanisms 1861(2): 80–94

  • Ptaszyńska-Sarosiek I, Dunaj J, Zajkowska A et al (2019) Post-mortem detection of six human herpesviruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6) in trigeminal and facial nerve ganglia by PCR. PeerJ 6:e6095

    Article  Google Scholar 

  • Rocha EM, De Miranda B, Sanders H (2017) Alpha-synuclein: pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurobiol Dis 109:249–257

    Article  Google Scholar 

  • Shukla S, Tekwani BL (2020) Histone deacetylases inhibitors in neurodegenerative diseases. Neuroprotection and Neuronal Differentiation Front Pharmacol 11:537

    CAS  PubMed  Google Scholar 

  • Spencer B, Potkar R, Trejo M, Rockenstein E, Patrick C, Gindi R,1 Adame A, Wyss-Coray T, and Masliah E (2009) Beclin 1 Gene transfer activates autophagy and ameliorates the neurodegenerative pathology in α-synuclein models of Parkinson’s and Lewy body diseases. The Journal of Neuroscience 29(43) 13578 13588

  • Sulzer D (2007) Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease. Trends Neurosci 30(5):244–250

    Article  CAS  Google Scholar 

  • Surmeier DJ (2018) Determinants of dopaminergic neuron loss in Parkinson’s disease. The Febs Journal 285:3657–3668

    Article  CAS  Google Scholar 

  • Tulisiak C, Mercado G, Peelaerts W, Brundin L, Brundin P (2019) Can infections trigger alpha-synucleinopathies? Prog Mol Biol Transl Sci 168:299–322

    Article  CAS  Google Scholar 

  • Valor LM, Viosca J, Lopez-Atalaya JP, Barco A (2013) Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders. Curr Pharm Des 19(28):5051

  • Xue, Yongming & Wen, Hong & Shi, Xiaobing (2018) CBP/p300: Intramolecular and intermolecular regulations. Frontiers in Biology

  • Yu WH, Dorado B, Figueroa H, Wang L, Planel E, Cookson M, Clark L, Duff K (2009) Metabolic activity determines efficacy of macroautophagic clearance of pathological oligomeric α-synuclein. Am J Pathol 175(2):736–747

  • 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

    Article  Google Scholar 

  • Zhu W, Swaminathan G, Plowey E (2014) GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes. Autophagy 10(9):1622–1636

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. The Center for the Biology of Chronic Disease (CBCD), 3 Germay Dr, Wilmington, DE, 19804, USA

    Hanan Polansky & Gillad Lori

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  1. Hanan Polansky
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  2. Gillad Lori
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Correspondence to Hanan Polansky.

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Polansky, H., Lori, G. How microcompetition with latent viruses can cause α synuclein aggregation, mitochondrial dysfunction, and eventually Parkinson’s disease. J. Neurovirol. 27, 52–57 (2021). https://doi.org/10.1007/s13365-020-00929-x

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