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Current Psychopharmacology

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ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

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Review Article

Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise

Author(s): Bernard W. Downs*, Steve Kushner, Manashi Bagchi, Kenneth Blum, Rajendra D. Badgaiyan, Sanjoy Chakraborty and Debasis Bagchi

Volume 10, Issue 2, 2021

Published on: 22 January, 2021

Page: [123 - 137] Pages: 15

DOI: 10.2174/2211556010666210122145526

Abstract

Background: Conventional medical therapies for neurodegenerative diseases primarily target anti-inflammatory interventions, immune suppression of autoimmune pathologies, and, depending on the diagnosed pathological mechanisms, neurotransmitter reuptake inhibition, among other tactics. However, the incidence of neuroinflammatory pathologies appears to be progressively increasing. The National Institutes of Health, National Institute of Environmental Health Sciences in 2016, estimated that 5.4 million Americans were living with Alzheimer's. If no effective solutions are found and implemented, within 30 years of this publication, according to data from Harvard, more than 12 million Americans will suffer from neurodegenerative diseases.

Methods: Rather than investigating greater etiological depth, modern medicine seems to have been designed to addressing obvious symptomologies to relieve suffering for as long as possible until neuropathological progress inevitably wins in achieving complete functional disability and death. Researchers are reporting herein evidence-based effective treatment therapies that are outside conventional medical standard of care therapies.

Conclusion: These therapies are the result of a deeper exploration into etiological factors, including an expanded understanding of the role of anaerobic pathologies in the etiology of neuroinflammatory disorders and methods of reverting to a competent aerobic metabolism. Such therapies include a liquid VMP35 MNC; a greater focus on viral mechanistic pathologies and their remission; and understanding of the genetic basis for a loss of neurological interconnectivity and consequential reward deficiencies in combination with neuronutrient deficiencies, enabling neuronutrient repletion with nutrigenomic therapies such as the KB220Z.

Keywords: Neuroinflammation, neurodegeneration, oxidative stress, cytokines, aerobic pathology, autophagy, Herpes virus, phytonutrients.

Graphical Abstract

[1]
Hollander JA, Lawler C. Neurodegenerative diseases. Available at: https://www.niehs.nih.gov/research/supported/health/neurodegenerative/index.cfm
[2]
Harvard NeuroDiscovery Center. The challenge of neurodegenerative diseases. Available at: https://neurodiscovery.harvard.edu/challenge
[3]
Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G. Neuroinflammation pathways: a general review. Int J Neurosci 2017; 127(7): 624-33.
[http://dx.doi.org/10.1080/00207454.2016.1212854] [PMID: 27412492]
[4]
Kumar A, Bagchi D, Eds. Antioxidants and functional foods for neurodegenerative disorders: uses in prevention and therapy. Boca Raton: CRC Press/Taylor & Francis 2020; pp. 1-510.
[http://dx.doi.org/10.1201/9780429319310]
[5]
Gibson GE, Starkov A, Blass JP, Ratan RR, Beal MF. Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases. Biochim Biophys Acta 2010; 1802(1): 122-34.
[http://dx.doi.org/10.1016/j.bbadis.2009.08.010] [PMID: 19715758]
[6]
Yao C, El Khoury R, Wang W, et al. LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson’s disease. Neurobiol Dis 2010; 40(1): 73-81.
[http://dx.doi.org/10.1016/j.nbd.2010.04.002] [PMID: 20382224]
[7]
Lim J, Yue Z. Neuronal aggregates: formation, clearance, and spreading. Dev Cell 2015; 32(4): 491-501.
[http://dx.doi.org/10.1016/j.devcel.2015.02.002] [PMID: 25710535]
[8]
Austin S, St-Pierre J. PGC1α and mitochondrial metabolism-emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 2012; 125(Pt 21): 4963-71.
[http://dx.doi.org/10.1242/jcs.113662] [PMID: 23277535]
[9]
Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L. Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neurosci Ther 2009; 15(1): 65-75.
[http://dx.doi.org/10.1111/j.1755-5949.2008.00065.x] [PMID: 19228180]
[10]
Labzin LI, Heneka MT, Latz E. Innate immunity and neurodegeneration. Annu Rev Med 2018; 69: 437-49.
[http://dx.doi.org/10.1146/annurev-med-050715-104343] [PMID: 29106805]
[11]
Shi Y, Holtzman DM. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat Rev Immunol 2018; 18(12): 759-72.
[http://dx.doi.org/10.1038/s41577-018-0051-1] [PMID: 30140051]
[12]
Castanon N, Luheshi G, Layé S. Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity. Front Neurosci 2015; 9: 229.
[http://dx.doi.org/10.3389/fnins.2015.00229] [PMID: 26190966]
[13]
Newcombe EA, Camats-Perna J, Silva ML, Valmas N, Huat TJ, Medeiros R. Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease. J Neuroinflammation 2018; 15(1): 276.
[http://dx.doi.org/10.1186/s12974-018-1313-3] [PMID: 30249283]
[14]
Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science 2016; 353(6301): 777-83.
[http://dx.doi.org/10.1126/science.aag2590] [PMID: 27540165]
[15]
Lee KM, MacLean AG. New advances on glial activation in health and disease. World J Virol 2015; 4(2): 42-55.
[http://dx.doi.org/10.5501/wjv.v4.i2.42] [PMID: 25964871]
[16]
Huang Y, Todd N, Thathiah A. The role of GPCRs in neurodegenerative diseases: avenues for therapeutic intervention. Curr Opin Pharmacol 2017; 32: 96-110.
[http://dx.doi.org/10.1016/j.coph.2017.02.001] [PMID: 28288370]
[17]
Azam S, Haque ME, Jakaria M, Jo S-H, Kim I-S, Choi D-K. G-protein-coupled receptors in CNS: a potential therapeutic target for intervention in neurodegenerative disorders and associated cognitive deficits. Cells 2020; 9(2): 506.
[http://dx.doi.org/10.3390/cells9020506] [PMID: 32102186]
[18]
Kawahara K, Hohjoh H, Inazumi T, Tsuchiya S, Sugimoto Y. Prostaglandin E2-induced inflammation: relevance of prostaglandin E receptors. Biochim Biophys Acta 2015; 1851(4): 414-21.
[http://dx.doi.org/10.1016/j.bbalip.2014.07.008] [PMID: 25038274]
[19]
Yang W, Xiong G, Lin B. Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa. J Neuroinflammation 2020; 17(1): 306.
[http://dx.doi.org/10.1186/s12974-020-01993-0] [PMID: 33059704]
[20]
Norat P, Soldozy S, Sokolowski JD, et al. Mitochondrial dysfunction in neurological disorders: exploring mitochondrial transplantation. NPJ Regen Med 2020; 5(1): 22.
[http://dx.doi.org/10.1038/s41536-020-00107-x] [PMID: 33298971]
[21]
Clark IA, Alleva LM, Vissel B. The roles of TNF in brain dysfunction and disease. Pharmacol Ther 2010; 128(3): 519-48.
[http://dx.doi.org/10.1016/j.pharmthera.2010.08.007] [PMID: 20813131]
[22]
Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech 2017; 10(5): 499-502.
[http://dx.doi.org/10.1242/dmm.030205] [PMID: 28468935]
[23]
Wang R, Reddy PH. Role of glutamate and NMDA receptors in Alzheimer’s disease. J Alzheimers Dis 2017; 57(4): 1041-8.
[http://dx.doi.org/10.3233/JAD-160763] [PMID: 27662322]
[24]
Harman D. Alzheimer’s disease: role of aging in pathogenesis. Ann N Y Acad Sci 2002; 959: 384-95.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02109.x] [PMID: 11976212]
[25]
Corbier JR, Downs BW, Kushner S, Aloisio T, Bagchi D, Bagchi M. VMP35 MNC, a novel iron-free supplement, enhances cytoprotection against anemia in human subjects: a novel hypothesis. Food Nutr Res 2019; 63
[http://dx.doi.org/10.29219/fnr.v63.3410] [PMID: 31105509]
[26]
Corona JC. Role of oxidative stress and neuroinflammation in attention-deficit/hyperactivity disorder. Antioxidants 2020; 9(11): 1039.
[http://dx.doi.org/10.3390/antiox9111039] [PMID: 33114154]
[27]
Bagchi D, Kuszynski C, Balmoori J, Bagchi M, Stohs SJ. Hydrogen peroxide-induced modulation of intracellular oxidized states in cultured macrophage J774A.1 and neuroactive PC-12 cells, and protection by a novel grape seed proanthocyanidin extract. Phytother Res 1998; 12: 568-71.
[http://dx.doi.org/10.1002/(SICI)1099-1573(199812)12:8<568::AID-PTR360>3.0.CO;2-5]
[28]
Roychowdhury S, Wolf G, Keilhoff G, Bagchi D, Horn T. Grape seed proanthocyanidin extract (GSPE) protects glia against nitrosative/oxidative stress. Nitric Oxide 2001; 5: 137-49.
[http://dx.doi.org/10.1006/niox.2001.0335] [PMID: 11292363]
[29]
Bagchi D, Bagchi M, Stohs SJ, et al. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 2000; 148(2-3): 187-97.
[http://dx.doi.org/10.1016/S0300-483X(00)00210-9] [PMID: 10962138]
[30]
Ding W, Ding LJ, Li FF, Han Y, Mu L. Neurodegeneration and cognition in Parkinson’s disease: a review. Eur Rev Med Pharmacol Sci 2015; 19(12): 2275-81.
[PMID: 26166654]
[31]
Carreira BP, Santos DF, Santos AI, Carvalho CM, Araújo IM. Nitric oxide regulates neurogenesis in the hippocampus following seizures. Oxid Med Cell Longev 2015; 2015: 451512.
[http://dx.doi.org/10.1155/2015/451512] [PMID: 26587180]
[32]
Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 2018; 14(10): 576-90.
[http://dx.doi.org/10.1038/s41574-018-0059-4] [PMID: 30046148]
[33]
Minciullo PL, Catalano A, Mandraffino G, et al. Inflammaging and anti-inflammaging: the role of cytokines in extreme longevity. Arch Immunol Ther Exp (Warsz) 2016; 64(2): 111-26.
[http://dx.doi.org/10.1007/s00005-015-0377-3] [PMID: 26658771]
[34]
Kooman JP, Dekker MJ, Usvyat LA, et al. Inflammation and premature aging in advanced chronic kidney disease. Am J Physiol Renal Physiol 2017; 313(4): F938-50.
[http://dx.doi.org/10.1152/ajprenal.00256.2017] [PMID: 28701312]
[35]
Gonzalez LC, Ghadaouia S, Martinez A, Rodier F. Premature aging/senescence in cancer cells facing therapy: good or bad? Biogerontology 2016; 17(1): 71-87.
[http://dx.doi.org/10.1007/s10522-015-9593-9] [PMID: 26330289]
[36]
Volkow ND, Wang GJ, Fowler JS, et al. Measuring age-related changes in dopamine D2 receptors with 11C-raclopride and 18F-N-methylspiroperidol. Psychiatry Res 1996; 67(1): 11-6.
[http://dx.doi.org/10.1016/0925-4927(96)02809-0] [PMID: 8797238]
[37]
Maspi N, Abdoli A, Ghaffarifar F. Pro- and anti-inflammatory cytokines in cutaneous leishmaniasis: a review. Pathog Glob Health 2016; 110(6): 247-60.
[http://dx.doi.org/10.1080/20477724.2016.1232042] [PMID: 27660895]
[38]
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 2014; 69(Suppl. 1): S4-9.
[http://dx.doi.org/10.1093/gerona/glu057] [PMID: 24833586]
[39]
Chen AL, Blum K, Chen TJ, et al. Correlation of the Taq1 dopamine D2 receptor gene and percent body fat in obese and screened control subjects: a preliminary report. Food Funct 2012; 3(1): 40-8.
[http://dx.doi.org/10.1039/C1FO10089K] [PMID: 22051885]
[40]
Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest 2000; 117(4): 1162-72.
[http://dx.doi.org/10.1378/chest.117.4.1162] [PMID: 10767254]
[41]
Boshtam M, Asgary S, Kouhpayeh S, Shariati L, Khanahmad H. Aptamers against pro- and anti-inflammatory cytokines: a review. Inflammation 2017; 40(1): 340-9.
[http://dx.doi.org/10.1007/s10753-016-0477-1] [PMID: 27878687]
[42]
Spagnuolo C, Moccia S, Russo GL. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 2018; 153: 105-15.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.001] [PMID: 28923363]
[43]
Sen CK, Bagchi D. Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract. Mol Cell Biochem 2001; 216(1-2): 1-7.
[http://dx.doi.org/10.1023/A:1011053300727] [PMID: 11216853]
[44]
Bagyinszky E, Giau VV, Shim K, Suk K, An SSA, Kim S. Role of inflammatory molecules in the Alzheimer’s disease progression and diagnosis. J Neurol Sci 2017; 376: 242-54.
[http://dx.doi.org/10.1016/j.jns.2017.03.031] [PMID: 28431620]
[45]
Merrill JE, Murphy SP. Inflammatory events at the blood brain barrier: regulation of adhesion molecules, cytokines, and chemokines by reactive nitrogen and oxygen species. Brain Behav Immun 1997; 11(4): 245-63.
[http://dx.doi.org/10.1006/brbi.1997.0496] [PMID: 9512813]
[46]
Rahman I, Bagchi D, Eds. Inflammation, advancing age and nutrition research and clinical interventions. 1st ed. San Diego, California, USA: Elsevier/Academic Press 2013; pp. 1-394.
[47]
Chatterjee S, Jungraithmayr W, Bagchi D. Immunity and inflammation in health and disease: emerging roles of nutraceuticals and functional foods in immune support. 1st ed. Cambridge, Massachusetts, USA: Elsevier/Academic Press 2017; pp. 1-459.
[48]
Michigan Medicine. Electrolyte Panel. Available at: https://www.uofmhealth.org/health-library/tr6146#:~:text=An%20electrolyte%20panel%20is%20a,are%20found%20in%20the%20body
[49]
Balcı AK, Koksal O, Kose A, et al. General characteristics of patients with electrolyte imbalance admitted to emergency department. World J Emerg Med 2013; 4(2): 113-6.
[http://dx.doi.org/10.5847/wjem.j.issn.1920-8642.2013.02.005] [PMID: 25215103]
[50]
Electrolytes (Chapter 15) In: National Research Council (US) Committee on Diet and Health, ed. Diet and health: implications for chronic disease risk. National Research Council (US) Committee on diet and health 1989; 413-30. https://www.ncbi.nlm.nih.gov/books/NBK218743/pdf/Bookshelf_NBK218743.pdf
[51]
Sqambato F, Sqambato E, De Santo NG. Acques Loeb (1859-1924) and his forgotten contributions to electrolyte and acid-base physiology in the organism as a whole. J G Ital Nefrol 2016; 33(Suppl 66): S66.28.
[52]
Yoshida T, Shevkoplyas SS. Anaerobic storage of red blood cells. Blood Transfus 2010; 8(4): 220-36.
[http://dx.doi.org/10.2450/2010.0022-10] [PMID: 20967163]
[53]
Brown KA. Erythrocyte metabolism and enzyme defects. Lab Med 1996; 27(5): 329-33.
[http://dx.doi.org/10.1093/labmed/27.5.329]
[54]
Hamm LL, Nakhoul N, Hering-Smith KS. Acid-base homeostasis. Clin J Am Soc Nephrol 2015; 10(12): 2232-42.
[http://dx.doi.org/10.2215/CJN.07400715] [PMID: 26597304]
[55]
Reddy P, Mooradian AD. Clinical utility of anion gap in deciphering acid-base disorders. Int J Clin Pract 2009; 63(10): 1516-25.
[http://dx.doi.org/10.1111/j.1742-1241.2009.02000.x] [PMID: 19769708]
[56]
Thomas CP, Hamawi K. What is the role of acidemia and alkalemia in the pathogenesis of metabolic acidosis? Available at: https://www.medscape.com/answers/242975-154551/what-is-the-role-of-acidemia-and-alkalemia-in-the-pathogenesis-of-metabolic-acidosis
[57]
Hopkins E, Sharma S. Physiology, acid base balance Stat-Pearls. Treasure Island, FL: StatPearls Publishing 2021.
[58]
Phypers B, Pierce T. Lactate physiology in health and disease. Contin Educ Anaesth Crit Care Pain 2006; 6(3): 128-32.
[http://dx.doi.org/10.1093/bjaceaccp/mkl018]
[59]
Information Center for Sickle cell and Thalassemic disorder. An overview of hemoglobin. 2002. Available at: http://sickle.bwh.harvard.edu/hemoglobin.html
[60]
Schechter AN. Hemoglobin research and the origins of molecular medicine. Blood 2008; 112(10): 3927-38.
[http://dx.doi.org/10.1182/blood-2008-04-078188] [PMID: 18988877]
[61]
Nonoyama A, Garcia-Lopez A, Garcia-Rubio LH, Leparc GF, Potter RL. Hypochromicity in red blood cells: an experimental and theoretical investigation. Biomed Opt Express 2011; 2(8): 2126-43.
[http://dx.doi.org/10.1364/BOE.2.002126] [PMID: 21833353]
[62]
Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 2013; 17(2): 162-84.
[http://dx.doi.org/10.1016/j.cmet.2012.12.012] [PMID: 23395166]
[63]
Freitas-Simoes TM, Ros E, Sala-Vila A. Nutrients, foods, dietary patterns and telomere length: Update of epidemiological studies and randomized trials. Metabolism 2016; 65(4): 406-15.
[http://dx.doi.org/10.1016/j.metabol.2015.11.004] [PMID: 26975532]
[64]
Rizvi S, Raza ST, Mahdi F. Telomere length variations in aging and age-related diseases. Curr Aging Sci 2014; 7(3): 161-7.
[http://dx.doi.org/10.2174/1874609808666150122153151] [PMID: 25612739]
[65]
Carmona JJ, Michan S. Biology of healthy aging and longevity. Rev Invest Clin 2016; 68(1): 7-16.
[PMID: 27028172]
[66]
Turner KJ, Vasu V, Griffin DK. Telomere biology and human phenotype. Cells 2019; 8(1): 73.
[http://dx.doi.org/10.3390/cells8010073] [PMID: 30669451]
[67]
Blum K, Gold M, Modestino EJ, et al. Would induction of dopamine homeostasis via coupling genetic addiction risk score (GARS®) and pro-dopamine regulation benefit benzodiazepine use disorder (BUD)? J Syst Integr Neurosci 2018; 4: 4.
[http://dx.doi.org/10.15761/JSIN.1000195] [PMID: 31750006]
[68]
Blum K, Trachtenberg MC, Elliott CE, et al. Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE. Alcohol 1988; 5(6): 481-93.
[http://dx.doi.org/10.1016/0741-8329(88)90087-0] [PMID: 3072969]
[69]
Skaper SD, Facci L, Giusti P. Neuroinflammation, microglia and mast cells in the pathophysiology of neurocognitive disorders: a review. CNS Neurol Disord Drug Targets 2014; 13(10): 1654-66.
[http://dx.doi.org/10.2174/1871527313666141130224206] [PMID: 25470401]
[70]
McDonough A, Weinstein JR. Neuroimmune response in ischemic preconditioning. Neurotherapeutics 2016; 13(4): 748-61.
[http://dx.doi.org/10.1007/s13311-016-0465-z] [PMID: 27525700]
[71]
Jakob MO, Murugan S, Klose CSN. Neuro-immune circuits regulate immune responses in tissues and organ homeostasis. Front Immunol 2020; 11: 308.
[http://dx.doi.org/10.3389/fimmu.2020.00308] [PMID: 32265899]
[72]
Zhou L, Miranda-Saksena M, Saksena NK. Viruses and neurodegeneration. Virol J 2013; 10: 172.http://www.virologyj.com/content/10/1/172
[http://dx.doi.org/10.1186/1743-422X-10-172] [PMID: 23724961]
[73]
Maynard ND, Gutschow MV, Birch EW, Covert MW. The virus as metabolic engineer. Biotechnol J 2010; 5(7): 686-94.
[http://dx.doi.org/10.1002/biot.201000080] [PMID: 20665642]
[74]
Boehmer PE, Nimonkar AV. Herpes virus replication. IUBMB Life 2003; 55(1): 13-22.
[http://dx.doi.org/10.1080/1521654031000070645] [PMID: 12716057]
[75]
Chang TW. Herpes simplex virus infection. Int J Dermatol 1983; 22(1): 1-7.
[http://dx.doi.org/10.1111/j.1365-4362.1983.tb02103.x] [PMID: 6299983]
[76]
Rechenchoski DZ, Faccin-Galhardi LC, Linhares REC, Nozawa C. Herpesvirus: an underestimated virus. Folia Microbiol (Praha) 2017; 62(2): 151-6.
[http://dx.doi.org/10.1007/s12223-016-0482-7] [PMID: 27858281]
[77]
Zhang J, Liu H, Wei B. Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection. J Zhejiang Univ Sci B 2017; 18(4): 277-88.
[http://dx.doi.org/10.1631/jzus.B1600460] [PMID: 28378566]
[78]
Groves MJ. Genital Herpes: A Review. Am Fam Physician 2016; 93(11): 928-34.
[PMID: 27281837]
[79]
Gray F, Bélec L, Lescs MC, et al. Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome. Brain 1994; 117(Pt 5): 987-99.
[http://dx.doi.org/10.1093/brain/117.5.987] [PMID: 7953606]
[80]
Chrétien F, Gray F, Lescs MC, et al. Acute varicella-zoster virus ventriculitis and meningo-myelo-radiculitis in acquired immunodeficiency syndrome. Acta Neuropathol 1993; 86(6): 659-65.
[http://dx.doi.org/10.1007/BF00294307] [PMID: 8310822]
[81]
Wood D. Neurovirulence. Dev Biol Stand 1999; 101: 127-9.
[PMID: 10566785]
[82]
Kurtishi A, Rosen B, Patil KS, Alves GW, Møller SG. Cellular proteostasis in neurodegeneration. Mol Neurobiol 2019; 56(5): 3676-89.
[http://dx.doi.org/10.1007/s12035-018-1334-z] [PMID: 30182337]
[83]
Baldwin KJ, Cummings CL. Neuroinfectious disease. Herpesvirus infections of the nervous system. Continuum (Minneap Minn) 2018; 24(5): 1349-69.
[http://dx.doi.org/10.1212/CON.0000000000000661] [PMID: 30273243]
[84]
Kawaguchi Y. [Herpes simplex virus (HSV)]. Uirusu 2010; 60(2): 187-96. [Herpes simplex virus (HSV)].
[http://dx.doi.org/10.2222/jsv.60.187] [PMID: 21488332]
[85]
Yorimitsu T, Klionsky DJ. Autophagy: molecular machinery for self-eating. Cell Death Differ 2005; 12(Suppl. 2): 1542-52.
[http://dx.doi.org/10.1038/sj.cdd.4401765] [PMID: 16247502]
[86]
Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptations. Nat Cell Biol 2007; 9(10): 1102-9.
[http://dx.doi.org/10.1038/ncb1007-1102] [PMID: 17909521]
[87]
Orvedahl A, Levine B. Autophagy and viral neurovirulence. Cell Microbiol 2008; 10(9): 1747-56.
[http://dx.doi.org/10.1111/j.1462-5822.2008.01175.x] [PMID: 18503639]
[88]
Berger JR, Houff S. Neurological complications of herpes simplex virus type 2 infection. Arch Neurol 2008; 65(5): 596-600.
[http://dx.doi.org/10.1001/archneur.65.5.596] [PMID: 18474734]
[89]
Akhtar J, Shukla D. Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry. FEBS J 2009; 276(24): 7228-36.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07402.x] [PMID: 19878306]
[90]
Mettenleiter TC, Klupp BG, Granzow H. Herpesvirus assembly: a tale of two membranes. Curr Opin Microbiol 2006; 9(4): 423-9.
[http://dx.doi.org/10.1016/j.mib.2006.06.013] [PMID: 16814597]
[91]
Gold MS, Baron D, Bowirrat A, Blum K. Neurological correlates of brain reward circuitry linked to opioid use disorder (OUD): do homo sapiens acquire or have a reward deficiency syndrome? J Neurol Sci 2020; 418: 117137.
[http://dx.doi.org/10.1016/j.jns.2020.117137] [PMID: 32957037]
[92]
Freeman DJ, Wenerstrom G, Spruance SL. Treatment of recurrent herpes simplex labialis with topical butylated hydroxytoluene. Clin Pharmacol Ther 1985; 38(1): 56-9.
[http://dx.doi.org/10.1038/clpt.1985.134] [PMID: 2988845]
[93]
van Genderen IL, Brandimarti R, Torrisi MR, Campadelli G, van Meer G. The phospholipid composition of extracellular herpes simplex virions differs from that of host cell nuclei. Virology 1994; 200(2): 831-6.
[http://dx.doi.org/10.1006/viro.1994.1252] [PMID: 8178468]
[94]
Pontow SE, Kery V, Stahl PD. Mannose receptor. Int Rev Cytol 1992; 137B: 221-44.
[http://dx.doi.org/10.1016/s0074-7696(08)62606-6] [PMID: 1478821]
[95]
Stahl PD, Rodman JS, Miller MJ, Schlesinger PH. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci USA 1978; 75(3): 1399-403.
[http://dx.doi.org/10.1073/pnas.75.3.1399] [PMID: 274729]
[96]
Milone MC, Fitzgerald-Bocarsly P. The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses. J Immunol 1998; 161(5): 2391-9.
[PMID: 9725235]
[97]
Ponce NM, Pujol CA, Damonte EB, Flores ML, Stortz CA. Fucoidans from the brown seaweed Adenocystis utricularis: extraction methods, antiviral activity and structural studies. Carbohydr Res 2003; 338(2): 153-65.
[http://dx.doi.org/10.1016/S0008-6215(02)00403-2] [PMID: 12526839]
[98]
Jadhav P, Kapoor N, Thomas B, Lal H, Kshirsagar N. Antiviral potential of selected Indian medicinal (ayurvedic) plants against herpes simplex virus 1 and 2. N Am J Med Sci 2012; 4(12): 641-7.
[http://dx.doi.org/10.4103/1947-2714.104316] [PMID: 23272307]
[99]
Zandi K, Ramedani E, Mohammadi K, et al. Evaluation of antiviral activities of curcumin derivatives against HSV-1 in Vero cell line. Nat Prod Commun 2010; 5(12): 1935-8.
[http://dx.doi.org/10.1177/1934578X1000501220] [PMID: 21299124]
[100]
Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ. Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity. Virology 2008; 373(2): 239-47.
[http://dx.doi.org/10.1016/j.virol.2007.11.028] [PMID: 18191976]
[101]
Bourne KZ, Bourne N, Reising SF, Stanberry LR. Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2. Antiviral Res 1999; 42(3): 219-26.
[http://dx.doi.org/10.1016/S0166-3542(99)00020-0] [PMID: 10443534]
[102]
Chiang LC, Ng LT, Cheng PW, Chiang W, Lin CC. Antiviral activities of extracts and selected pure constituents of Ocimum basilicum. Clin Exp Pharmacol Physiol 2005; 32(10): 811-6.
[http://dx.doi.org/10.1111/j.1440-1681.2005.04270.x] [PMID: 16173941]
[103]
Verma H, Patil PR, Kolhapure RM, Gopalkrishna V. Antiviral activity of the Indian medicinal plant extract Swertia chirata against herpes simplex viruses: a study by in-vitro and molecular approach. Indian J Med Microbiol 2008; 26(4): 322-6.
[http://dx.doi.org/10.4103/0255-0857.43561] [PMID: 18974483]
[104]
Cheng HY, Lin TC, Yang CM, Wang KC, Lin LT, Lin CC. Putranjivain A from Euphorbia jolkinin, demonstrated inhibitory effect on HSV-2 in vitro. J Antimicrob Chemother 2004; 53: 577-83.
[http://dx.doi.org/10.1093/jac/dkh136] [PMID: 14998984]
[105]
Tolo FM, Rukunga GM, Muli FW, et al. Anti-viral activity of the extracts of a Kenyan medicinal plant Carissa edulis against herpes simplex virus. J Ethnopharmacol 2006; 104(1-2): 92-9.
[http://dx.doi.org/10.1016/j.jep.2005.08.053] [PMID: 16198524]
[106]
Li W, Wang XH, Luo Z, et al. Traditional Chinese medicine as a potential source for HSV-1 therapy by acting on virus or the susceptibility of host. Int J Mol Sci 2018; 19(10): 3266.
[http://dx.doi.org/10.3390/ijms19103266] [PMID: 30347851]
[107]
Hsu CM, Chiang ST, Chang YY, et al. Lychee flower extract inhibits proliferation and viral replication of HSV-1-infected corneal epithelial cells. Mol Vis 2016; 22: 129-37.
[PMID: 26937165]
[108]
Kuo YC, Lin YL, Liu CP, Tsai WJ. Herpes simplex virus type 1 propagation in HeLa cells interrupted by Nelumbo nucifera. J Biomed Sci 2005; 12(6): 1021-34.
[http://dx.doi.org/10.1007/s11373-005-9001-6] [PMID: 16132118]
[109]
Bisignano C, Mandalari G, Smeriglio A, et al. Almond skin extracts abrogate HSV-1 replication by blocking virus binding to the cell. Viruses 2017; 9(7): 178.
[http://dx.doi.org/10.3390/v9070178] [PMID: 28698509]
[110]
Hung PY, Ho BC, Lee SY, et al. Houttuynia cordata targets the beginning stage of herpes simplex virus infection. PLoS One 2015; 10(2): e0115475.
[http://dx.doi.org/10.1371/journal.pone.0115475] [PMID: 25643242]
[111]
Jiang X, Kinch LN, Brautigam CA, et al. Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity 2012; 36(6): 959-73.
[http://dx.doi.org/10.1016/j.immuni.2012.03.022] [PMID: 22705106]
[112]
Griffith RS, Norins AL, Kagan C. A multicentered study of lysine therapy in Herpes simplex infection. Dermatologica 1978; 156(5): 257-67.
[http://dx.doi.org/10.1159/000250926] [PMID: 640102]
[113]
Miller CS, Foulke CN. Use of lysine in treating recurrent oral herpes simplex infections. Gen Dent 1984; 32(6): 490-3.
[PMID: 6097505]
[114]
Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980; 60(1): 85-7.
[PMID: 6153847]
[115]
McCune MA, Perry HO, Muller SA, O’Fallon WM. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 1984; 34(4): 366-73.
[PMID: 6435961]
[116]
Griffith RS, DeLong DC, Nelson JD. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture. Chemotherapy 1981; 27(3): 209-13.
[http://dx.doi.org/10.1159/000237979] [PMID: 6262023]
[117]
Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 1987; 175(4): 183-90.
[http://dx.doi.org/10.1159/000248823] [PMID: 3115841]
[118]
Mailoo VJ, Rampes S. Lysine for Herpes Simplex Prophylaxis: a review of the evidence. Integr Med (Encinitas) 2017; 16(3): 42-6.
[PMID: 30881246]
[119]
DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol 1984; 120(1): 48-51.
[http://dx.doi.org/10.1001/archderm.1984.01650370054010] [PMID: 6419679]
[120]
Bagchi D, Downs BW, Bagchi M, Kushner S. A novel strategy for processing, production and quality control of an iron-free nutraceutical supplement that rapidly restores iron-dependent hemoglobin in red blood cells. Food Prod Process Nutr 2020; 2: 26.
[http://dx.doi.org/10.1186/s43014-020-00042-w]
[121]
Wang Q, Guo R, Nair S, et al. Safety and efficacy of N-SORB®, a proprietary KD120 MEC metabolically activated enzyme formulation: a randomized, double-blind, placebo-controlled study. J Am Coll Nutr 2019; 38(7): 577-85.
[http://dx.doi.org/10.1080/07315724.2019.1586591] [PMID: 30971174]
[122]
Blum K, Chen AL, Chen TJ, et al. LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome. Adv Ther 2008; 25(9): 894-913.
[http://dx.doi.org/10.1007/s12325-008-0093-z] [PMID: 18781289]
[123]
Blum K, Liu Y, Wang W, et al. rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med 2015; 127(2): 232-41.
[http://dx.doi.org/10.1080/00325481.2015.994879] [PMID: 25526228]
[124]
Febo M, Blum K, Badgaiyan RD, et al. Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z. PLoS One 2017; 12(4): e0174774.
[http://dx.doi.org/10.1371/journal.pone.0174774] [PMID: 28445527]
[125]
Blum K, Lott L, Baron D, Smith DE, Badgaiyan RD, Gold MS. Improving naltrexone compliance and outcomes with putative pro-dopamine regulator KB220, compared to treatment as usual J Syst Integr Neurosci 2020; 7: 10.15761.
[126]
Blum K, Gondré-Lewis MC, Modestino EJ, et al. Understanding the scientific basis of post-traumatic stress disorder (PTSD): precision behavioral management overrides stigmatization. Mol Neurobiol 2019; 56(11): 7836-50.
[http://dx.doi.org/10.1007/s12035-019-1600-8] [PMID: 31124077]
[127]
McLaughlin T, Blum K, Oscar-Berman M, et al. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. J Behav Addict 2015; 4(2): 106-15.
[http://dx.doi.org/10.1556/2006.4.2015.008] [PMID: 26132915]
[128]
Modestino EJ, Blum K, Oscar-Berman M, et al. Reward deficiency syndrome: attentional/arousal subtypes, limitations of current diagnostic nosology, and future research. J Reward Defic Syndr 2015; 1(1): 6-9.
[http://dx.doi.org/10.17756/jrds.2015-002] [PMID: 26306327]
[129]
Blum K, Oscar-Berman M, Badgaiyan RD, Khurshid KA, Gold MS. Dopaminergic neurogenetics of sleep disorders in reward deficiency syndrome (RDS). J Sleep Disord Ther 2014; 3(2): 126.
[http://dx.doi.org/10.4172/2167-0277.1000e126] [PMID: 25657892]
[130]
Blum K, Thanos PK, Wang GJ, et al. The food and drug addiction epidemic: targeting dopamine homeostasis. Curr Pharm Des 2018; 23(39): 6050-61.
[http://dx.doi.org/10.2174/1381612823666170823101713] [PMID: 28831923]
[131]
McLaughlin T, Blum K, Steinberg B, et al. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD. J Behav Addict 2018; 7(1): 192-203.
[http://dx.doi.org/10.1556/2006.6.2017.081] [PMID: 29316800]
[132]
Mclaughlin T, Oscar-Berman M, Simpatico T, et al. Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette’s syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT). J Behav Addict 2013; 2(2): 117-24.
[http://dx.doi.org/10.1556/JBA.2.2013.2.8] [PMID: 26165932]
[133]
Blum K, Whitney D, Fried L, et al. Hypothesizing that a pro-dopaminergic regulator (kb220z™ liquid variant) can induce “dopamine homeostasis” and provide adjunctive detoxification benefits in opiate/opioid dependence. Clin Med Rev Case Rep 2016; 3(8): 125.
[http://dx.doi.org/10.23937/2378-3656/1410125] [PMID: 29034323]
[134]
Blum K, Chen TJ, Morse S, et al. Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D₂ agonist therapy: part 2. Postgrad Med 2010; 122(6): 214-26.
[http://dx.doi.org/10.3810/pgm.2010.11.2237] [PMID: 21084796]
[135]
Blum K, Oscar-Berman M, Braverman ER, Febo M, Li M, Gold MS. Enhancing brain pregnenolone may protect cannabis intoxication but should not be considered as an anti-addiction therapeutic: hypothesizing dopaminergic blockade and promoting anti-reward. J Reward Defic Syndr 2015; 1(1): 20-3.
[http://dx.doi.org/10.17756/jrds.2015-005] [PMID: 26306328]
[136]
Miller DK, Bowirrat A, Manka M, et al. Acute intravenous synaptamine complex variant KB220™ “normalizes” neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms: part 1, pilot study with 2 case reports. Postgrad Med 2010; 122(6): 188-213.
[http://dx.doi.org/10.3810/pgm.2010.11.2236] [PMID: 21084795]
[137]
Solanki N, Abijo T, Galvao C, Darius P, Blum K, Gondré-Lewis MC. Administration of a putative pro-dopamine regulator, a neuronutrient, mitigates alcohol intake in alcohol-preferring rats. Behav Brain Res 2020; 385: 112563.
[http://dx.doi.org/10.1016/j.bbr.2020.112563] [PMID: 32070691]
[138]
Gyollai A, Griffiths MD, Barta C, et al. The genetics of problem and pathological gambling: a systematic review. Curr Pharm Des 2014; 20(25): 3993-9.
[http://dx.doi.org/10.2174/13816128113199990626] [PMID: 24001288]
[139]
Miller M, Chen AL, Stokes SD, et al. Early intervention of intravenous KB220IV--neuroadaptagen amino-acid therapy (NAAT) improves behavioral outcomes in a residential addiction treatment program: a pilot study. J Psychoactive Drugs 2012; 44(5): 398-409.
[http://dx.doi.org/10.1080/02791072.2012.737727] [PMID: 23457891]
[140]
Blum K, Cull JG, Chen TJH, Garcia-Swan S, Holder J. Clinical evidence For Effectiveness of Phencal™ in maintaining weight loss in an open-label, controlled, 2-year study. Curr Therap Res 1997; 58(10)
[141]
Chen TJ, Blum K, Waite RL, et al. Gene Attenuation Program attenuates substance use disorder, a clinical subtype of reward deficiency syndrome. Adv Ther 2007; 24(2): 402-14.
[http://dx.doi.org/10.1007/BF02849910] [PMID: 17565932]
[142]
Blum K, Modestino JE, Gondre-Lewis MC, et al. Pro-dopamine regulator (kb220) a fifty year sojourn to combat reward deficiency syndrome (rds): evidence based bibliography (annotated). CPQ Neurol Psychol 2018; 1(2) https://www.cientperiodique.com/journal/fulltext/CPQNP/1/2/13
[143]
Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 1991; 48(7): 648-54.
[http://dx.doi.org/10.1001/archpsyc.1991.01810310066012] [PMID: 2069496]
[144]
Blum K, Febo M, McLaughlin T, Cronjé FJ, Han D, Gold SM. Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric. J Behav Addict 2014; 3(3): 149-56.
[http://dx.doi.org/10.1556/JBA.3.2014.019] [PMID: 25317338]
[145]
Fried L, Modestino EJ, Siwicki D, et al. Hypodopaminergia and “Precision Behavioral Management” (PBM): it is a generational family affair. Curr Pharm Biotechnol 2020; 21(6): 528-41.
[http://dx.doi.org/10.2174/1389201021666191210112108] [PMID: 31820688]
[146]
McLaughlin T, Han D, Nicholson J, et al. Improvement of long-term memory access with a pro-dopamine regulator in an elderly male: are we targeting dopamine tone? J Syst Integr Neurosci 2017; 3(3)
[http://dx.doi.org/10.15761/JSIN.1000165] [PMID: 29423319]
[147]
Blum K, Braverman ER, Dinardo MJ, Wood RC, Sheridan PJ. Prolonged P300 latency in a neuropsychiatric population with the D2 dopamine receptor A1 allele. Pharmacogenetics 1994; 4(6): 313-22.
[http://dx.doi.org/10.1097/00008571-199412000-00004] [PMID: 7704037]
[148]
Barr CL, Kidd KK. Population frequencies of the A1 allele at the dopamine D2 receptor locus. Biol Psychiatry 1993; 34(4): 204-9.
[http://dx.doi.org/10.1016/0006-3223(93)90073-M] [PMID: 8399816]
[149]
Abijo T, Blum K, Gondré-Lewis MC. Neuropharmacological and neurogenetic correlates of Opioid Use Disorder (OUD) as a function of ethnicity: relevance to precision addiction medicine. Curr Neuropharmacol 2020; 18(7): 578-95.
[http://dx.doi.org/10.2174/1570159X17666191118125702] [PMID: 31744450]
[150]
Blum K, Badgaiyan RD, Dunston GM, et al. The DRD2 Taq1A A1 allele may magnify the risk of Alzheimer’s in aging African-Americans. Mol Neurobiol 2018; 55(7): 5526-36.
[http://dx.doi.org/10.1007/s12035-017-0758-1] [PMID: 28965318]
[151]
Steinberg B, Blum K, McLaughlin T, et al. Low-resolution electromagnetic tomography (LORETA) of changed brain function provoked by pro-dopamine regulator (KB220z) in one adult ADHD case. Open J Clin Med Case Rep 2016; 2(11): 1121.
[PMID: 27610420]
[152]
Downs B, Oscar-Berman M, Waite R, et al. Have we hatched the addiction egg: reward deficiency syndrome solution system™. J Genet Syndr Gene Ther 2013; 4(136): 14318.
[http://dx.doi.org/10.4172/2157-7412.1000136] [PMID: 24077767]
[153]
Thundyil J, Lim KL. DAMPs and neurodegeneration. Ageing Res Rev 2015; 24(Pt A): 17-28.
[http://dx.doi.org/10.1016/j.arr.2014.11.003]
[154]
Blum K, Oscar-Berman M, Stuller E, et al. Neurogenetics and nutrigenomics of neuro-nutrient therapy for reward deficiency syndrome (rds): clinical ramifications as a function of molecular neurobiological mechanisms. J Addict Res Ther 2012; 3(5): 139.
[http://dx.doi.org/10.4172/2155-6105.1000139] [PMID: 23926462]

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