Abstract
Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association.
Discussion: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer’s and Parkinson’s disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients.
Conclusion: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.
Keywords: BDNF, homeostasis, neurodegenerative disorders, BDNF/TrkB cascade, alternative therapy, Alzheimer's disease.
[1]
Mehler MF, Kessler JA. Growth factor regulation of neuronal development. Developmental Neurosci 16(3-4): 180-95. (1994).
[2]
Trujillo CA, Schwindt TT, Martins AH, Alves JM, Mello LE, Ulrich H. Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics. Cytometry Part A: J Intl Soc Analy Cytol 75(1): 38-53. (2009).
[3]
Oliveira SL, Pillat MM, Cheffer A, Lameu C, Schwindt TT, Ulrich H. Functions of neurotrophins and growth factors in neurogenesis and brain repair. Cytometry A 83(1): 76-89. (2013).
[4]
Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10(3): 209-19. (2011).
[5]
Gupta VK, You Y, Gupta VB, Klistorner A, Graham SL. TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci 14(5): 10122-42. (2013).
[6]
Carlino D, De Vanna M, Tongiorgi E. Is altered BDNF biosynthesis a general feature in patients with cognitive dysfunctions? The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 19(4): 345-53. (2013).
[7]
Radin DP, Patel P. BDNF: an oncogene or tumor suppressor? Anticancer Res 37(8): 3983-90. (2017).
[8]
Glazner GW, Mattson MP. Differential effects of BDNF, ADNF9, and TNFalpha on levels of NMDA receptor subunits, calcium homeostasis, and neuronal vulnerability to excitotoxicity. Exp Neurol 161(2): 442-52. (2000).
[9]
Driver JA. Inverse association between cancer and neurodegenerative disease: review of the epidemiologic and biological evidence. Biogerontology 15(6): 547-57. (2014).
[10]
Feng YA, Cho K, Lindstrom S, Kraft P, Cormack J, Liang L, et al. Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics. Hum Genet 136(10): 1341-51. (2017).
[12]
Cahn BR, Goodman MS, Peterson CT, Maturi R, Mills PJ. Yoga, meditation and mind-body health: increased bdnf, cortisol awakening response, and altered inflammatory marker expression after a 3-month yoga and meditation retreat. Front Hum Neurosci 11: 315. (2017).
[13]
Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway. Cell Metab 18(5): 649-59. (2013).
[14]
Driver JA, Beiser A, Au R, Kreger BE, Splansky GL, Kurth T. et al. Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ 344: e1442. (2012).
[15]
Roe CM, Fitzpatrick A, Xiong C, Sieh W, Kuller L, Miller J, et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74(2): 106-12. (2010).
[16]
Li JM, Liu C, Hu X, Cai Y, Ma C, Luo XG, et al. Inverse correlation between Alzheimer’s disease and cancer: implication for a strong impact of regenerative propensity on neurodegeneration? BMC Neurol 14: 211. (2014).
[17]
Driver JA, Kurth T, Buring JE, Gaziano JM, Logroscino G. Prospective case-control study of nonfatal cancer preceding the diagnosis of Parkinson’s disease. Cancer Causes Control 18(7): 705-11. (2007).
[18]
Xie X, Luo X, Xie M. Association between Parkinson’s disease and risk of colorectal cancer. Parkinsonism Relat Disord 35: 42-7. (2017).
[19]
W Nixon D. The inverse relationship between cancer and Alzheimer’s Disease: a possible mechanism. Curr Alzheimer Res 14(8): 883-93. (2017).
[20]
Yu H, Zhang Z, Shi Y, Bai F, Xie C, Qian Y, et al. Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han. J Clin Psychiatry 69(7): 1104-11. (2008).
[21]
Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 7(5): 695-702. (1991).
[22]
Laske C, Stransky E, Leyhe T, Eschweiler GW, Wittorf A, Richartz E, et al. Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm 113(9): 1217-24. (2006).
[23]
Holsinger RM, Schnarr J, Henry P, Castelo VT, Fahnestock M. Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease. Brain Res Mol Brain Res 76(2): 347-54. (2000).
[24]
Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M. Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Brain Res Mol Brain Res 49(1-2): 71-81. (1997).
[25]
Laske C, Stransky E, Leyhe T, Eschweiler GW, Maetzler W, Wittorf A, et al. BDNF serum and CSF concentrations in Alzheimer’s disease, normal pressure hydrocephalus and healthy controls. J Psychiatr Res 41(5): 387-94. (2007).
[26]
Peng S, Wuu J, Mufson EJ, Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem 93(6): 1412-21. (2005).
[27]
Howells DW, Porritt MJ, Wong JY, Batchelor PE, Kalnins R, Hughes AJ, et al. Reduced BDNF mRNA expression in the Parkinson’s disease substantia nigra. Exp Neurol 166(1): 127-35. (2000).
[28]
Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, et al. Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett 270(1): 45-8. (1999).
[29]
Parain K, Murer MG, Yan Q, Faucheux B, Agid Y, Hirsch E, et al. Reduced expression of brain-derived neurotrophic factor protein in Parkinson’s disease substantia nigra. Neuroreport 10(3): 557-61. (1999).
[30]
Sohrabji F, Lewis DK. Estrogen-BDNF interactions: implications for neurodegenerative diseases. Front Neuroendocrinol 27(4): 404-14. (2006).
[31]
Ciammola A, Sassone J, Cannella M, Calza S, Poletti B, Frati L, et al. Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington’s disease patients. Am J Med Genet 144b(4): 574-7. (2007).
[32]
Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Müller F-J, Loring JF, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Nat Acad Sci P106(32): 13594-9. (2009).
[33]
Caccamo A, Maldonado MA, Bokov AF, Majumder S, Oddo S. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer’s disease. Proc Nat Acad Sci 107(52): 22687-92. (2010).
[34]
Banik A, Prabhakar S, Kalra J, Anand A. Effect of human umbilical cord blood derived lineage negative stem cells transplanted in amyloid-β induced cognitive impaired mice. Behav Brain Res 291: 46-59. (2015).
[35]
Choi SH, Bylykbashi E, Chatila ZK, Lee SW, Pulli B, Clemenson GD, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science 361(6406) (2018).
[36]
Rantamäki T, Kemppainen S, Autio H, Staven S, Koivisto H, Kojima M, et al. The impact of Bdnf gene deficiency to the memory impairment and brain pathology of APPswe/PS1dE9 mouse model of Alzheimer’s disease. PLoS One 8(7): e68722. (2013).
[37]
Jiao S, Shen L, Zhu C, Bu X, Liu Y, Liu C, et al. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl Psychiatry 6(10): e907. (2016).
[38]
Baghestani AR, Daneshvar T, Pourhoseingholi MA, Asadzade H. Survival of colorectal cancer patients in the presence of competing-risk. Asian Pac J Cancer Prev 15(15): 6253-5. (2014).
[39]
Yang X, Martin TA, Jiang WG. Biological influence of brain-derived neurotrophic factor (BDNF) on colon cancer cells. Exp Ther Med 6(6): 1475-81. (2013).
[40]
Huang SM, Lin C, Lin HY, Chiu CM, Fang CW, Liao KF, et al. Brain-derived neurotrophic factor regulates cell motility in human colon cancer. Endocrine-related Can 22(3): 455-64. (2015).
[41]
Tichy JR, Lim E, Anders CK. Breast cancer in adolescents and young adults: a review with a focus on biology. J Natl Compr Canc Netw 11(9): 1060-9. (2013).
[42]
Hondermarck H. Neurotrophins and their receptors in breast cancer. Cytokine Growth Factor Rev 23(6): 357-65. (2012).
[43]
Patani N, Jiang WG, Mokbel K. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer. Cancer Cell Int 11(1): 23. (2011).
[44]
Bronzetti E, Artico M, Forte F, Pagliarella G, Felici L, D’Ambrosio A, et al. A possible role of BDNF in prostate cancer detection. Oncol Rep 19(4): 969-74. (2008).
[45]
Lai PC, Chiu TH, Huang YT. Overexpression of BDNF and TrkB in human bladder cancer specimens. Oncol Rep 24(5): 1265-70. (2010).
[46]
Yang X, Martin TA, Jiang WG. Biological influence of brain-derived neurotrophic factor on breast cancer cells. Int J Oncol 41(4): 1541-6. (2012).
[47]
Tajbakhsh A, Mokhtari-Zaer A, Rezaee M, Afzaljavan F, Rivandi M, Hassanian SM, et al. Therapeutic potentials of BDNF/TrkB in breast cancer; current status and perspectives. J Cell Biochem 118(9): 2502-15. (2017).
[48]
Tsai YF, Tseng LM, Hsu CY, Yang MH, Chiu JH, Shyr YM. Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer. PLoS One 12(6): e0178173. (2017).
[49]
Puehringer D, Orel N, Lüningschrör P, Subramanian N, Herrmann T, Chao MV, et al. EGF transactivation of Trk receptors regulates the migration of newborn cortical neurons. Nat Neurosci 16(4): 407. (2013).
[50]
Chen B, Liang Y, He Z, An Y, Zhao W, Wu J. Autocrine activity of BDNF induced by the STAT3 signaling pathway causes prolonged TrkB activation and promotes human non-small-cell lung cancer proliferation. Sci Rep 6: 30404. (2016).
[51]
Au CW, Siu MK, Liao X, Wong ES, Ngan HY, Tam KF, et al. Tyrosine kinase B receptor and BDNF expression in ovarian cancers–Effect on cell migration, angiogenesis and clinical outcome. Cancer Lett 281(2): 151-61. (2009).
[52]
Kawamura K, Kawamura N, Mulders SM, Gelpke MDS, Hsueh AJ. Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos. Proc Natl Acad Sci USA 102(26): 9206-11. (2005).
[53]
Kang HJ, Kim JM, Kim SY, Kim SW, Shin IS, Kim HR, et al. A longitudinal study of BDNF promoter methylation and depression in breast cancer. Psychiatry Investig 12(4): 523-31. (2015).
[54]
Lai PC, Chiu TH, Huang YT. Overexpression of BDNF and TrkB in human bladder cancer specimens. Oncol Rep 24(5): 1265-70. (2010).
[55]
Okamura K, Harada T, Wang S, Ijichi K, Furuyama K, Koga T, et al. Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer. Lung Cancer (Amsterdam, Netherlands) 78(1): 100-6. (2012).
[56]
Bronzetti E, Artico M, Forte F, Pagliarella G, Felici LM, D’Ambrosio A, et al. A possible role of BDNF in prostate cancer detection. Oncol Rep 19(4): 969-74. (2008).
[57]
Tanaka K, Okugawa Y, Toiyama Y, Inoue Y, Saigusa S, Kawamura M, et al. Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer. PLoS One 9(5): e96410. (2014).
[58]
Kimura S, Harada T, Ijichi K, Tanaka K, Liu R, Shibahara D, et al. Expression of brain-derived neurotrophic factor and its receptor TrkB is associated with poor prognosis and a malignant phenotype in small cell lung cancer. Lung Cancer (Amsterdam, Netherlands) 120: 98-107. (2018).
[59]
Au CW, Siu MK, Liao X, Wong ES, Ngan HY, Tam KF, et al. Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome. Cancer Lett 281(2): 151-61. (2009).
[60]
Cohen L, Warneke C, Fouladi RT, Rodriguez MA, Chaoul-Reich A. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma Cancer100(10): 2253-60 (2004).
[61]
Saligan L, Lukkahatai N, Holder G, Walitt B, Machado-Vieira R. Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy. World J Biol Psychiatry 17(8): 608-14. (2016).
[62]
Ng T, Lee YY, Chae J-w, Yeo AHL, Shwe M, Gan YX, et al. Evaluation of plasma brain-derived neurotrophic factor levels and self-perceived cognitive impairment post-chemotherapy: a longitudinal study. BMC Cancer 17(1): 867. (2017).
[63]
Naveen G, Thirthalli J, Rao M, Varambally S, Christopher R, Gangadhar B. Positive therapeutic and neurotropic effects of yoga in depression: a comparative study. Int J Psychiatry 55(Suppl. 3): S400. (2013).
[64]
Tolahunase M, Sagar R, Dada R. Impact of yoga and meditation on cellular aging in apparently healthy individuals: a prospective, open-label single-arm exploratory study. Oxid Med Cell Longev 2017: 7928981. (2017).
[65]
Tolahunase M, Sagar R, Dada R. Erratum to “impact of yoga and meditation on cellular aging in apparently healthy individuals: a prospective, open-label single-arm exploratory study”. Oxidative medicine and cellular longevity 2017. (2017).
[66]
Konar A, Shah N, Singh R, Saxena N, Kaul SC, Wadhwa R, et al. Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells. PLoS One 6(11): e27265. (2011).
[67]
Shah N, Kataria H, Kaul SC, Ishii T, Kaur G, Wadhwa R. Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation. Cancer Sci 100(9): 1740-7. (2009).
[68]
Pandareesh M, Anand T. Neuromodulatory propensity of Bacopa monniera against scopolamine-induced cytotoxicity in PC12 cells via down-regulation of AChE and up-regulation of BDNF and muscarnic-1 receptor expression. Cell Mol Neurobiol 33(7): 875-84. (2013).
[69]
Hazra S, Kumar S, Saha GK, Mondal AC. Reversion of BDNF, Akt and CREB in hippocampus of chronic unpredictable stress induced rats: effects of phytochemical, Bacopa Monnieri. Psychiatry Investig 14(1): 74-80. (2017).
[70]
Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X, et al. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Res 1122(1): 56-64. (2006).
[71]
Liu D, Wang Z, Gao Z, Xie K, Zhang Q, Jiang H, et al. Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behav Brain Res 271: 116-21. (2014).
[72]
Foster PP. Role of physical and mental training in brain network configuration. Front Aging Neurosci 7: 117. (2015).
[73]
Zimmer P, Baumann FT, Oberste M, Schmitt J, Joisten N, Hartig P, et al. Influence of personalized exercise recommendations during rehabilitation on the sustainability of objectively measured physical activity levels, fatigue, and fatigue-related biomarkers in patients with breast cancer. Integr Cancer Ther 1534735417713301. (2017).
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Diabetes Reviews
Current Neuropharmacology
Current Neurovascular Research
Central Nervous System Agents in Medicinal Chemistry
Current Respiratory Medicine Reviews
Current Pediatric Reviews
Infectious Disorders - Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets
Current Stem Cell Research & Therapy
Related Books
Frontiers in Clinical Drug Research-Dementia
COVID-19: Causes, Transmission, Diagnosis, and Treatment
Skeletal Muscle Health in Metabolic Diseases
Thyroid and Brain: Understanding the Actions of Thyroid Hormones in Brain Development and Function
Common Lip Diseases: A Clinical Guide
Interventional Pain Surgery
Endoscopy and Fetoscopy Techniques for the Brain and Neuroaxis
Frontiers in Stem Cell and Regenerative Medicine Research
Textbook of Advanced Dermatology: Pearls for Academia and Skin Clinics (Part 2)
Women’s Health: A Comprehensive Guide to Common Health Issues in Women
Article Metrics
56
8
1
1