Please wait a minute...
Journal of Integrative Neuroscience  2020, Vol. 19 Issue (1): 187-199    DOI: 10.31083/j.jin.2020.01.3
Special Issue: Genetics of neurological diseases
Mini-Review Previous articles | Next articles
Neurodegenerative diseases and cancer: sharing common mechanisms in complex interactions
Natalia González Rojas1, Martin Cesarini1, José Luis Etcheverry1, Gustavo Andrés Da Prat1, 2, Valeria Antico Arciuch3, Emilia Mabel Gatto1, 2, *()
1Instituto Neurociencias Buenos Aires (INEBA), Guardia Vieja 4435, CABA, Argentina
2Sanatorio de la Trinidad Mitre, Bartolomé Mitre 2553, CABA, Argentina
3Conicet, Godoy Cruz 2290, CABA, Argentina
Download:  PDF(1318KB)  ( 998 ) Full text   ( 73 )
Export:  BibTeX | EndNote (RIS)      
Abstract  

Several epidemiological studies support low cancer rates in patients with neurodegenerative disorders, including Parkinson's disease, Huntington's disease, and Alzheimer's disease. Different mechanisms were raised as possible causes, from mutated tumor suppressor genes (PARKIN, PINK1) to small interfering RNA based on the CAG trinucleotide repeat expansions located in introns or untranslated regions. However, as every rule has an exception, some tumors have an increased incidence in these neurodegenerative diseases such as breast and skin cancer (melanoma). This mini-review aims to establish the epidemiology between these neurodegenerative disorders and cancer to determine the possible mechanisms involved and therefore set eventual therapeutic applications. According to our findings, we conclude the presence of an inverse relationship among most cancers and the aforementioned neurodegenerative disorders. However, this concept needs to be considered cautiously considering specific genetic and extra-genetic linkage factors for particular tumors.

Key words:  Parkinson’s disease      Huntington’s disease      Alzheimer’s disease      neurodegenerative disorders      cancer      mechanisms     
Submitted:  06 January 2020      Accepted:  27 March 2020      Published:  30 March 2020     
*Corresponding Author(s):  Emilia Mabel Gatto     E-mail:  emiliamgatto@gmail.com

Cite this article: 

Natalia González Rojas, Martin Cesarini, José Luis Etcheverry, Gustavo Andrés Da Prat, Valeria Antico Arciuch, Emilia Mabel Gatto. Neurodegenerative diseases and cancer: sharing common mechanisms in complex interactions. Journal of Integrative Neuroscience, 2020, 19(1): 187-199.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2020.01.3     OR     https://jin.imrpress.com/EN/Y2020/V19/I1/187

Table 1  Observed cancer cases vs. expected ones in an HD population (Coarelli et al., 2017).
TYPE OF CANCER CASES EXPECTED
Breast 8 14.22
Skin 5 0.98
Bladder 2 4.52
Prostate 1 5.96
Cervix 1 4.48
Figure 1.  Aging results in increased levels of metabolic disturbances, loss of proteostasis, oxidative stress, and DNA damage leading to genomic instability. Many of these aging disturbances are involved in neurodegeneration and cancer and contribute to the development of both disorders.

Figure 2.  Schematic representation of the AMPK-Parkin pathway and the negative regulation of necroptosis and tumorigenesis via RIPK3 inhibition. Parkin reduces cancer-induced inflammation and leads to the inhibitory mechanism of necroptosis. Necrosome complex conformation requires the RIPK1 kinase activation to promote the binding to phosphorylated RIPK3. The complex RIPK1/RIPK3 induces AMPK activation that, in turn, phosphorylates and activates Parkin leading to RIPK3 ubiquitylation. This process inhibits necrosome conformation and prevents necroptosis and cancer-induced inflammation.

Figure 3.  Parkinson’s disease and cancer, Parkin mediated mechanisms. A scheme on the role of PARKIN in the development of cancer. The decreased expression of PARKIN lowers the expression of the tumor suppressor gene PTEN, leading to an increase in proinflammatory interleukins (IL-1b; TNF-a), increasing the rate of cancer development. On the other hand, the overexpression of PARKIN leads to a decreased expression of endothelial growth factor receptor (VEGFR), inducing the stabilization of microtubules and leading to an anti-inflammatory and antitumor effect.

Figure 4.  Overlapping biological pathways of PD and cancer mainly include protein accumulation, mitochondrial damage, oxidative stress response, chronic inflammation, and cell cycle control with flaws in DNA repair. This scheme shows how the three most common genes Parkin, DJ-1, and PINK1 involved in PD lead to dysregulation of both tumor suppressor genes, PTEN, and P53.

Figure 5.  Flow charts of the canonical pathway of mutant Htt to miRNA. In the nucleus, primary microRNAs are cleaved by Drosha complex in precursor microRNA (pre-miRNA), The pre-miRNA is exported to the cytoplasm by Exportin-5. At the cytoplasm, pre-miRNA is processed by Dicer complex into double-stranded loop RNAs, mature microRNA (mature miRNA). The strand with the more unstable 5′-end is selected for loading onto miRNA-induced silencing complex (miRISC). RISC., -bound miRNAs to modulate miRNA activity (degradation and/or translational suppression). Finally, miRNA shows a regulatory role in different pathological pathways involving tumor cells.

Figure 6.  Role of the Huntingtin-associated protein 1 (HAP1) and mutant huntingtin interaction in traffic of organelles and protein regulation. Huntingtin is a scaffold protein with a capacity to bind to a HAP1 protein, which modulates the binding to dynactin or kinesin proteins (microtubule protein complex). The dynactin complex promotes retrograde trafficking, while kinesin promotes anterograde trafficking towards the synaptic area.

Figure 7.  Common pathways to the three neurodegenerative diseases (Huntington’s disease HD, Parkinson’s disease PD and Alzheimer’s disease AD) leading the activation of the P53 gene, with the consequent antioxidant effect and, as a final pathway, the apoptosis of neoplastic cells. P53, a transcriptional factor, has shown multiple functions in the crossroads among cancer and neurodegenerative disorders such as HD, PD, and AD. p53 demonstrates a central role in the balance of cell cycle arrest-DNA repair and programmed death, maintaining a delicate balance between cancer suppressive and age-promoting functions.

Figure 8.  Role of Phosphodiesterase 10A (PDE10A) in the cAMP signaling cascade PDE10A mediated intracellular signaling by hydrolyzing the ATP to the cAMP. Increased levels of cAMP promote activation of protein kinase A (PKA) that, in turn, modulates Dopamine-and cAMP-Regulated Phosphoprotein, Mr 32 kDa (DARPP-32) phosphorylation leading the promotion of neuronal survival by genes regulation.

[1] Abdel-Magid, A. F. (2019) LRRK2 kinase inhibitors as possible therapy for Parkinson’s disease and other neurodegenerative disorders. ACS Medicinal Chemistry Letters 10, 846-847.
[2] Alvarez-Erviti, L., Rodriguez-Oroz, M. C., Cooper, J. M., Caballero, C., Ferrer, I., Obeso, J. A. and Schapira, A. H. (2010) Chaperone-mediated autophagy markers in Parkinson's disease brains. JAMA Neurology 67, 1464-1472.
[3] Alvin, P., Joselin, S. J., Hewitt, S. M., Kim, R. H., Chung, Y. H., Mak, T. W., Shen, J., Slack, R. S. and Park, D. S. (2012) ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons. Human Molecular Genetics 21, 4888-4903.
[4] Bae, B. I., Xu, H., Igarashi, S., Fujimuro, M., Agrawal, N., Taya, Y., Hayward, S. D., Moran, T. H., Montell, C., Ross, C. A., Snyder, S. H. and Sawa, A. (2005) P53 mediates cellular dysfunction and behavioral abnormalities in Huntington’s disease. Neuron 47, 29-41.
[5] Bennett, D. A. and Leurgans, S. (2010) Is there a link between cancer and Alzheimer disease? Neurology 74, 100-101.
[6] Bertoni, J. M., Arlette, J. P., Fernandez, H. H., Fitzer-Attas, C., Frei, K., Hassan, M. N., Isaacson, S. H., Lew, M. F., Lew, E., Ondo, W. G., Phillips, T. J., Singer, C., Sutton, J. P. and Wolf Jr, J. E. (2010) Increased melanoma risk in Parkinson disease: a prospective clinicopathological study. JAMA Neurology 67, 347-352.
[7] Bjørg, J. and Aasly, J. O. (2018) Exploring cancer in LRRK2 mutation carriers and idiopathic Parkinson’s disease. Brain and Behavior 8, e00858.
[8] Boursi, B., Mamtani, R., Haynes, K. and Yang, Y. X. (2016) Parkinson’s disease and colorectal cancer risk-a nested case control study. Cancer Epidemiology 43, 9-14.
[9] Cao, K. and Tait, S. W. (2019) Parkin inhibits necroptosis to prevent cancer. Nature Cell Biology 21, 915-923.
[10] Cesari, R., Martin, E. S., Calin, G. A., Pentimalli, F., Bichi, R., McAdams, H., Trapasso, F., Drusco, A., Shimizu, M., Masciullo, V., D'Andrilli, G., Scambia, G., Picchio, M. C., Alder, H., Godwin, A. K. and Croce, C. M. (2003) Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proceedings of the National Academy of Sciences of the United States of America 100, 5956-5961.
[11] Chan, J. H. and Chan, S. H. (2015) Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1. Pharmacology & Therapeutics 156, 69-74.
[12] Cheung, Z. H. and Ip, N. Y. (2009) The emerging role of autophagy in Parkinson’s disease. Molecular Brain 2, 29.
[13] Coarelli, G., Diallo, A., Thion, M. S., Rinaldi, D., Calvas, F., Boukbiza, O. L., Tataru, A., Charles, P., Tranchant, C., Marelli, C., Ewenczyk, C., Tchikviladzé, M., Monin, M. L., Carlander, B., Anheim, M., Brice, A., Mochel, F., Tezenas du Montcel, S., Humbert, S. and Durr, A. (2017) Low cancer prevalence in polyglutamine expansion diseases. Neurology 88, 1-6.
[14] Constantinescu, R. and Kieburtz, R. M. (2006) The DATATOP Parkinson study group investigators. Malignant melanoma in early Parkinson’s disease-DATATOP trial. Movement Disorders 22, 720-722.
[15] Demetrius, L. A. and Driver, J. A. (2015) Preventing Alzheimer’s disease by means of natural selection. Journal of the Royal Society Interface 12, 20140919.
[16] Denison, S. R., Wang, F., Becker, N. A, Schüle, B., Kock, N., Phillips, L. A., Klein, C. and Smith, D. I. (2003) Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene 22, 8370-8378.
[17] Driver, J. A. (2012) Understanding the link between cancer and neurodegeneration. Journal of Geriatric Oncology 3, 58-67.
[18] Driver, J. A., Beiser, A., Au, R., Kreger, B. E., Splansky, G. L., Kurth, T., Kiel, D. P., Lu, K. P., Seshadri, S. and Wolf, P. A. (2012) Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. British Medical Journal 2012,344.
[19] Elbaz, A., Peterson, B. J., Bower, J. H., Yang, P., Maraganore, D. M., McDonnell, S. K., Ahlskog, J. E. and Rocca, W. A. (2005) Risk of cancer after the diagnosis of Parkinson’s disease: a historical cohort study. Movement Disorders 20, 719-725.
[20] Engel, P. A. (2016) Is age-related failure of metabolic reprogramming a principal mediator in idiopathic Parkinson’s disease? Implications for treatment and inverse cancer risk. Medical Hypotheses 93, 154-160.
[21] Gargini, R., Segura-Collar, B. and Sánchez-Gómez, P. (2019) Novel functions of the neurodegenerative-related gene tau in cancer. Frontiers in Aging Neuroscience 11, 231.
[22] Goodwin, M. (2005) MBNL sequestration by toxic RNAs and RNA misprocessing in the myotonic dystrophy brain. Cell Reports 12, 1159-1168.
[23] Haque, M. E., Thomas, K. J.,D'Souza, C. Callaghan, S., Kitada, T., Slack, R. S., Fraser, P., Cookson, M. R., Tandon, A. and Park, D. S. (2008) Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP. Proceedings of the National Academy of Sciences of the United States of America 105, 1716-1721.
[24] Ho, T. H., Savkur, R, S., Poulos, M, G., Mancini, M. A., Swanson, M. S. and Cooper, T. A. (2016) Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy. Journal of Cell Science 118, 2923-2933.
[25] Hoehn, M. M. and Yahr, M. D. (1967) Parkinsonism: onset, progression and mortality. Neurology 17, 427-442.
[26] Houck, A. L., Seddighi, S. and Driver, J. A. (2018) At the crossroads between neurodegeneration and cancer: A review of overlapping biology and its implications. Current Aging Science 11, 77-89.
[27] Hosgood, H. D., Menashe, I., Shen, M., Yeager, M., Yuenger, J., Rajaraman, P., He, X., Chatterjee, N., Caporaso, N. E., Zhu, Y., Chanock, S. J., Zheng, T. and Lan, Q. (2008) Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway. Carcinogenesis 29, 1938-1943.
[28] Hussain, S. P. and Harris, C. (2007) Inflammation and cancer: an ancient link with novel potentials. International Journal of Cancer 121, 2373-2380.
[29] Inzelberg, R. and Jankovic, J. (2007) Are Parkinson disease patients protected from some but not all cancers? Neurology 69, 1-1.
[30] Jansson, B. and Jankovic, J. (1985) Low cancer rates among patients with Parkinson's disease. Annals of Neurology 17, 505-509.
[31] Kalchman, M. A., Koide, H. B., McCutcheon, K., Graham, R. K., Nichol, K., Nishiyama, K., Kazemi-Esfarjani, P., Lynn, F. C., Wellington, C., Metzler, M., Goldberg, Y. P., Kanazawa, I., Gietz, R. D. and Hayden, M. R. (1997) HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nature Genetics 16, 44-53.
[32] Kerbel, R. S and Kamen, B. A. (2004) The anti-angiogenic basis of metronomic chemotherapy. Nature Reviews Cancer 4, 423-436.
[33] Kim, R. H., Peters, M., Jang, Y., Shi, W., Pintilie, M., Fletcher, G. C., DeLuca, C., Liepa, J., Zhou, L., Snow, B., Binari, R. C., Manoukian, A. S., Bray, M. R., Liu, F. F., Tsao, M. S. and Mak, T. W. (2005) DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 7, 263-273.
[34] Kim, Y. C., Kitaura, H., Taira, T., Iguchi-Ariga, S. M. and Ariga, H. (2009) Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN. International Journal of Oncology 35, 1331-1341.
[35] Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y. and Shimizu, N. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608.
[36] Ko, H. S., von Coelln, R., Sriram, S. R., Kim, S. W., Chung, K. K., Pletnikova, O., Troncoso, J., Johnson, B., Saffary, R., Goh, E. Krol, J. (2007) Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Molecular Cell 25, 575-586.
[37] Kotecha, S., Lebot, M. N., Sukkarn, B., Ball, G., Moseley, P. M., Chan, S. Y., Green, A. R., Rakha, E., Ellis, I. O., Martin, S. G. and Storr, S. J. (2019) Dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression. Scientific Reports 9, 16987.
[38] Krol, J. (2007) Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Molecular Cell 25, 575-586.
[39] Kumar, A., Vaish, M. and Ratan, R. R. (2014) Transcriptional dysregulation in Huntington’s disease: a failure of adaptive transcriptional homeostasis. Drug Discovery Today 19, 956-962.
[40] Lane, C., Hardy, J. and Schott, J. M. (2018) Alzheimer's disease. European Journal of Neurology 25, 59-70.
[41] Lee, S. B., Kim, J. J., Han, S. A., Fan, Y., Guo, L., Aziz, K., Nowsheen, S., Kim, S. S., Park, S., Luo, Q., Chung, J. O., Choi, S., Aziz, A., Yin, P., Tong, S., Fiesel, F. C., Springer, W., Zhang, J. and Lou, Z. (2019) The AMPK-Parkin axis negatively regulates necroptosis andtumorigenesis by inhibiting the necrosome. Nature Cell Biology 21, 940-951.
[42] Lee, S., She, J., Deng, B., Kim, J., de Andrade, M., Na, J., Sun, Z., Wampfler, J. A., Cunningham, J. M., Wu, Y., Limper, A. H., Aubry, M. C., Wendt, C., Biterman, P., Yang, P. and Lou, Z. (2016) Multiple-level validation identifies PARK2 in the development of lung cancer and chronic obstructive pulmonary disease. Oncotarget 2016, 44211-44223.
[43] Leupold, D., Szyc, L., Stankovic, G., Strobel, S., Völker, H. U., Fleck, U., Müller, T., Scholz., M., Riederer, P. and Monoranu, C. M. (2019) Melanin and neuromelanin fluorescence studies focusing on Parkinson’s disease and its inherent risk for melanoma. Cells 8, 592.
[44] Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S. H., Giovanella, B. C., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M. H. and Parsons, R. (1997) PTEN, a putative protein tyrosine phosphatasegene mutated in human brain, breast, and prostate cancer. Science 275, 1943-1947.
[45] Li, N., Lee, K., Xi, Y., Zhu, B., Gary, B. D., Ramírez-Alcántara, V., Gurpinar, E., Canzoneri, J. C., Fajardo, A., Sigler, S., Piazza, J. T., Chen, X., Andrews, J., Thomas, M., Lu, W., Li, Y., Laan, D. J., Moyer, M. P., Russo, S., Eberhardt, B. T., Yet, L., Keeton, A. B., Grizzle, W. E. and Piazza, G. A. (2015) Phosphodiesterase 10A: a novel target for selective inhibition of colon tumor cell growth and β-catenin-dependent TCF transcriptional activity. Oncogene 34, 1499-1509.
[46] Li, X. J., Li, S. H., Sharp, A, H., Nucifora, F. C. Jr., Schilling, G., Lanahan, A., Worley, P., Snyder, S. H. and Ross, C. A. (1995) A huntingtin-associated protein enriched in brain with implications for pathology. Nature 378, 398-402.
[47] Lin, L., Park, J. W., Ramachandran, S., Zhang, Y., Tseng, Y. T., Shen, S., Waldvogel, H. J., Curtis, M. A., Faull, R. L., Troncoso, J. C., Pletnikova, O., Ross, C. A., Davidson, B. L. and Xing, Y. (2016) Transcriptome sequencing reveals aberrant alternative splicing in Huntington’s disease. Human Molecular Genetics 25, 3454-3466.
[48] Louis, P., Hold, G. L. and Flint, H. J. (2014) The gut microbiota, bacterial metabolites and colorectal cancer. Nature Reviews Microbiology 12, 661-672.
[49] Maries, E., Dass, B., Collier, T. J. and Steece-Collier, K. (2003) The role of alphasynuclein in Parkinson’s disease: insights from animal models. Nature Reviews Neuroscience 4, 727-738.
[50] Ma, S. L., Tang, N. L., Tam, C. W., Lui, V. W., Lam, L. C., Chiu, H. F., Driver, J. A., Pastorino, L. and Lu, K. P. (2012) A PIN1 polymorphism that prevents its suppression by AP4 associates with delayed onset of Alzheimer’s disease. Neurobiology of Aging 33, 804-813.
[51] McColgan, P. and Tabrizi, S. J. (2018) Huntington’s disease: a clinical review. European Journal of Neurology 25, 24-34.
[52] McNulty, P., Pilcher, R., Ramesh, R., Necuiniate, R., Hughes, A., Farewell, D., Holmans, P., Jones, L. and REGISTRY Investigators of the European Huntington’s Disease Network. (2018) Reduced cancer incidence in Huntington’s disease: Analysis in the registry study. Journal of Huntington’s Disease 7, 209-222.
[53] Millikin, D., Meese, E. and Vogelstein, B. (1991) Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma. Cancer Research 51, 5449-5453.
[54] Morales-Briceño, H., Cervantes-Arriaga, A. and Rodríguez-Violante, M. (2011) Diagnóstico premotor de la enfermedad de Parkinson. Gaceta Médica de México (in Spanish) 147, 22-32.
[55] Murmann, A. E., Yu, J., Opal, P. and Peter, N. E. (2018) Trinucleotide repeat expansion diseases, RNAi, and cancer. Cell press: Trends in Cancer 4, 684-700.
[56] Murmann, A. E. (2018) Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells. EMBO Reports 19, e45336.
[57] Nalavade, R. (2013) Mechanisms of RNA-induced toxicity in CAG repeat disorders. Cell Death & Disease 4, e752.
[58] Nelson, D. L. (2013) The unstable repeats-three evolving faces of neurological disease. Neuron 77, 825-843.
[59] Nutt, J. G. and Wooten, G. F. (2005) Diagnosis and initial management of Parkinson’s disease. The New England Journal of Medicine 353, 1021-1027.
[60] O'Flanagan, C. H. and O'Neill, C. (2014) PINK1 signalling in cancer biology. Biochimica et Biophysica Acta 1846, 590-598.
[61] Okereke, O. I. and Meadows, M. E. (2019) More Evidence of an Inverse Association Between Cancer and Alzheimer Disease. JAMA Network Open 2, e196167.
[62] Olsen, J. H., Friis, S. and Frederiksen, K. (2006) Malignant melanoma and other types ofcancer preceding Parkinson disease. Epidemiology 17, 582-587.
[63] Ospina-Romero, M., Abdiwahab, E., Kobayashi, L., Filshtein, T., Brenowitz, W. D., Mayeda, E. R. and Glymour, M. M. (2019) Rate of Memory Change Before and After Cancer Diagnosis. JAMA Network Open 2, e196160.
[64] Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A. and Schneider, S. A. (2009) Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Annals of Neurology 65, 19-23.
[65] Pan, T., Kondo, S., Le, W. and Jankovic, J. (2008) The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson’s disease. Brain 131, 1969-1978.
[66] Pan, T., Li, X. and Jankovic, J. (2011) The association between Parkinson’s disease and melanoma. International Journal of Cancer 128, 2251-2260.
[67] Pan, T., Zhu, J., Hwu, W. J. and Jankovic, J. (2012) The role of Alpha-Synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells. PLOS ONE 7, e45183.
[68] Pagan, F. L., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Arellano, J., Howard, H. H., Peyton, M., Matar, S., Liu, X., Fowler, A. J., Schwartz, S. L., Ahn, J. and Moussam, C. (2019a) Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease. Pharmacology Research & Perspectives 7, e00470.
[69] Pagan, F. L., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Anjum, M., Arellano, J., Howard, H. H., Shi, W., Mulki, S., Kurd-Misto, T., Matar, S., Liu, X., Ahn, J. and Moussa, C. (2019b) Nilotinib effects on safety, tolerability, and potential biomarkers in Parkinson Disease: A phase 2 randomized clinical trial. JAMA Neurology 77, 309-317.
[70] Palacino, J. J., Sagi, D. and Goldberg, M. S. (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. The Journal of Biological Chemistry 279, 18614-18622.
[71] Pavliukeviciene, B., Zentelyte, A., Jankunec, M., Valiuliene, G., Talaikis, M., Navakauskiene, R., Niaura, G. and Valincius, G. (2019) Amyloid β oligomers inhibit growth of human cancer cells. Research Article. PLOS ONE 14, e0221563.
[72] Pfützner, W. and Przybilla, B. (1997) Malignant melanoma and levodopa: is there a relationship? Two new cases and a review of the literature. Journal of the American Academy of Dermatology 37, 332-336.
[73] Picchio, M. C., Martin, E. S., Cesari, R., Calin, G. A., Yendamuri, S., Kuroki, T., Pentimalli, F., Sarti, M., Yoder, K., Kaiser, L. R., Fishel, R. and Croce, C. M. (2004) Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clinical Cancer Research 10, 2720-2724.
[74] Plun-Favreau, H., Lewis, P. A., Hardy, J., Martins, L. M. and Wood, N. W. (2010) Cancer and Neurodegeneration: Between the devil and the deep blue sea. PLOS Genetics 6, e1001257.
[75] Polymeropoulos, M. H., Lavedan, C., Leroy, E. Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G, Lazzarini, A. M., Duvoisin, R. C., Di Iorio, G., Golbe, L. I. and Nussbaum, R. L. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276, 2045-2047.
[76] Przybilla, B., Schwab, U., Landthaler, M. and Braun-Falco, O. (1985) Development of two malignant melanomas during administration of levodopa. Acta Dermato-Venereologica 65, 556-567.
[77] Qiu, Z. (2006) Sp1 is up-regulated in cellular and transgenic models of Huntington disease, and its reduction is neuroprotective. Journal of Biological Chemistry 281, 16672-16680.
[78] Ong, E. L., Goldacre, R. and Goldacre, M. (2014) Differential risks of cancer types in people with Parkinson's disease: a national record-linkage study. European Journal of Cancer 50, 2456-2462.
[79] Ren, Y., Jiang, H., Yang, F., Nakaso, K. and Feng, J. (2009) Parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation. The Journal of Biological Chemistry 284, 4009-4017.
[80] Roe, C. M., Fitzpatrick, A. L., Xiong, C., Sieh, W., Kuller, L., Miller, J. P., Williams, M. M., Kopan, R., Behrens, M. I. and Morris, J. C. (2010) Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74, 106-112.
[81] Rom, O., Avezov, K. and Aizenbud, D. (2013) Cigarette smoking and inflammation revisited. Respiratory Physiology & Neurobiology 187, 5-10.
[82] Rugbjerg, K., Christensen, J., Tjønneland, A. and Olsen, J. H. (2013) Exposure to estrogen and women’s risk for Parkinson’s disease: A prospective cohort study in Denmark. Parkinsonism & Related Disorders 19, 457-460.
[83] Sandyk, R. (1992) Accelerated growth of malignant melanoma by levodopa in Parkinson’s disease and role of the pineal gland. International Journal of Neuroscience 63, 137-140.
[84] Sarkar, C., Chakroborty, D. and Dasgupta, P. S. (2015) Dopamine is a safe antiangiogenic drug which can also prevent 5-fluorouracil induced neutropenia. International Journal of Cancer 137, 744-749.
[85] Schmidt, S., Linnartz, B., Mendritzki, S., Sczepan, T., Lübbert, M., Stichel, C. C. and Lübbert, H. (2011) Genetic mouse models for Parkinson’s disease display severe pathology in glial cell mitochondria. Human Molecular Genetics 20, 1197-1211.
[86] Segat, L., Pontillo, A., Annoni, G., Trabattoni, D., Vergani, C., Clerici, M., Arosio, B. and Crovella, S. (2007) PIN1 promoter polymorphisms are associated with Alzheimer’s disease. Neurobiology of Aging 28, 69-74.
[87] Sherwood, L. M., Parris, E. E. and Folkman, J. (1971) Tumor angiogenesis: therapeutic implications. The New England Journal of Medicine 285, 1182-1186.
[88] Skibba, J. L., Pinckley, J. and Gilbert, E. F. (1972) Multiple primary melanoma following administration of levodopa. Archives of Pathology & Laboratory Medicine 93, 556-561.
[89] Song, L. H., Park, B. J., Kim, M. J., Kim, S., Dawson, V. L. and Dawson, T. M. (2005) Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. Journal of Neuroscience 25, 7968-7978.
[90] Thion, M. S., Tézenas du Montcel, S., Golmard, J. L., Vacher, S., Barjhoux, L., Sornin, V., Cazeneuve, C., Bièche, I., Sinilnikova, O., Stoppa-Lyonnet, D., Durr, A. and Humbert, S. (2016) CAG repeat size in Huntingtin alleles is associated withcancer prognosis. European Journal of Human Genetics 24, 1310-1315.
[91] Thomas, K. J., McCoy, M. K., Blackinton, J., Beilina, A., van der Brug, M., Sandebring, A., Miller, D., Maric, D., Cedazo-Minguez, A., Cookson, M. R. (2011) DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Human Molecular Genetics 20, 40-50.
[92] Tief, K., Schmidt, A. and Beermann, F. (1998) New evidence for presence of tyrosinase in substantia nigra, forebrain and midbrain. Molecular Brain Research 53, 307-310.
[93] Turner, M. R., Goldacre, R. and Goldacre, M. J. (2012) Letter to the Editor: Reduced cancer incidence in Huntington’s disease: record linkage study clue to an evolutionary trade-off? Clinical Genetics 83, 588-590.
[94] Vanacore, N., Spila-Alegiani, S., Raschetti, R. and Meco, G. (1999) Mortality cancer risk in parkinsonian patients: a population-based study. Neurology 52, 395-398.
[95] Van Heemst, D., Mooijaart, S. P., Beekman, M., Schreuder, J., de Craen, A. J., Brandt, B. W., Slagboom, P. E., Westendorp, R. G. and Long Life study group. (2005) Variation in the human TP53 gene affects old age survival and cancer mortality. Experimental Gerontology 40, 11-15.
[96] Wakabayashi, K., Tanji, K. and Mori, F. (2007) The Lewy body in Parkinson’s disease: molecules implicated in the formation and degradation of a-synuclein aggregates. Neuropathology 27, 494-506.
[97] Wahabi, K., Perwez, A. and Rizvi, M. A. (2018) Parkin in Parkinson’s disease and cancer: a double-edged sword. Molecular Neurobiology 55, 6788-6800.
[98] Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M. and Heldin, C. H. (1994) Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. The Journal of Biological Chemistry 269, 26988-26995.
[99] Wang, F., Denison, S., Lai, J. P., Philips, L. A., Montoya, D., Kock, N., Schüle, B., Klein, C., Shridhar, V., Roberts, L. R., Smith, D. I. (2004) Parkin gene alterations in hepatocellular carcinoma. Genes Chromosomes Cancer 40, 85-96.
[100] Wojciechowska, M. and Krzyzosiak, W. J. (2011) Cellular toxicity of expanded RNA repeats: focus on RNA foci. Human Molecular Genetics 20, 3811-3821.
[101] Wood, H. (2015) Changes in brain phosphodiesterase 10A levels in neurodegenerative basal ganglia disorders. Nature Reviews Neurology 11, 483-483.
[102] Wu, X., Senechal, K., Neshat, M. S., Whang, Y. E. and Sawyers, C. L. (1998) The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proceedings of the National Academy of Sciences of the United States of America 95, 15587-15591.
[103] Xie, X., Luo, X. and Xie, M. (2016) Association between Parkinson's disease and risk of colorectal cancer.Parkinsonism and Related Disorders. Parkinsonism & Related Disorders 35, 42-47.
[104] Xu, L., Lin, D., Yin, D. and Koeffler, H. P. (2014) An emerging role of PARK2 in cancer. Journal of Molecular Medicine 92, 31-42.
[105] Xu, Y., Stokes, A. H., Freeman, W. M., Kumer, S. C., Vogt, B. A. and Vrana, K. E. (1997) Tyrosinase mRNA is expressed in human substantia nigra. Molecular Brain Research 45, 159-162.
[106] Yamamoto, A., Friedlein, A., Imai, Y., Takahashi, R., Kahle, P. J. and Haass, C. (2005) Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity. The Journal of Biological Chemistry 280, 3390-3399.
[107] Yang, F., Jiang, Q., Zhao, J., Ren, Y., Sutton, M. D. and Feng, J. (2005) Parkin stabilizes microtubules through strong binding mediated by three independent domains. The Journal of Biological Chemistry 280, 17154-17162.
[108] Zekeridou, A., Kryzer, T., Guo, Y., Hassan, A., Lennon, V., Lucchinetti, C. F., Pittock, S. and McKeon, A. (2019) Phosphodiesterase 10A IgG.A novel biomarker of paraneoplastic neurologic autoimmunity. Neurology 93, 815-822.
[109] Zhu, L., Song, X., Tang, J., Wu, J., Ma, R., Cao, H., Ji, M., Jing, C. and Wang, Z. (2013) Huntingtin-associated protein 1: A potential biomarker of breast cancer. Oncology Reports 29, 1881-1887.
[1] Yan-Jie Chen, Yuan-Jin Chan, Wen-Jing Chen, Ya-Ming Li, Chun-Yan Zhang. Muramyl dipeptide promotes Aβ1-42 oligomer production via the nod2/p-p38 mapk/bace1 signaling pathway in the sh-sy5y cells[J]. Journal of Integrative Neuroscience, 2020, 19(3): 421-428.
[2] Jonathan Kuten, Adi Linevitz, Hedva Lerman, Nanette Freedman, Meir Kestenbaum, Tamara Shiner, Nir Giladi, Einat Even-Sapir. [18F] FDOPA PET may confirm the clinical diagnosis of Parkinson's disease by imaging the nigro-striatal pathway and the sympathetic cardiac innervation: Proof-of-concept study[J]. Journal of Integrative Neuroscience, 2020, 19(3): 489-494.
[3] Michael G. Z. Ghali, George Zaki Ghali, Adriana Lima, Michael McDermott, Emma Glover, Stefanos Voglis, Jennifer Humphrey, Marton Skog Steinberger König, Henry Brem, Per Uhlén, Robert F. Spetzler, M. Gazi Yasargil. Mechanisms underlying the generation of autonomorespiratory coupling amongst the respiratory central pattern generator, sympathetic oscillators, and cardiovagal premotoneurons[J]. Journal of Integrative Neuroscience, 2020, 19(3): 521-560.
[4] Jia-Hui Yan, Ping Hua, Yong Chen, Lan-Ting Li, Cui-Yu Yu, Lei Yan, Hui Zhang, Ying He, Hao Zheng, Hui Chen, Zhao-Jing Zhang, Qi-Hui Yao, Hui Dong, Wei-Guo Liu. Identification of microRNAs for the early diagnosis of Parkinson’s disease and multiple system atrophy[J]. Journal of Integrative Neuroscience, 2020, 19(3): 429-436.
[5] Jie Chen, Yunling Huang, Ling Li, Jie Niu, Weiqiong Ye, Yunnan Wang, Can Yan, Lili Wu. Antidepressant pathways of the Chinese herb jiaweisinisan through genetic ontology analysis[J]. Journal of Integrative Neuroscience, 2020, 19(2): 385-395.
[6] Lu Yu, Jie Tao, Qing Zhao, Chuan Xu, Qiujuan Zhang. Confirmation of potential neuroprotective effects of natural bioactive compounds from traditional medicinal herbs in cerebral ischemia treatment[J]. Journal of Integrative Neuroscience, 2020, 19(2): 373-384.
[7] Lan Zhou, Yu-Fang Huang, Hui Xie, Xiao-Yun Mei, Jun Cao. Herbal complex 'Buyang Huanwu Tang' improves motor endplate function of denervated-dependent skeletal muscle atrophy in rat[J]. Journal of Integrative Neuroscience, 2020, 19(1): 89-99.
[8] Qian Zhang, Jia Li, Wenqiang An, Yiou Fan, Qilong Cao. Neural stem cell secretome and its role in the treatment of neurodegenerative disorders[J]. Journal of Integrative Neuroscience, 2020, 19(1): 179-185.
[9] Heng Zhai, Zihua Kang, Haibo Zhang, Junjie Ma, Guangxin Chen. Baicalin attenuated substantia nigra neuronal apoptosis in Parkinson’s disease rats via the mTOR/AKT/GSK-3β pathway[J]. Journal of Integrative Neuroscience, 2019, 18(4): 423-429.
[10] Yangfei Ji, Dan Wang, Boai Zhang, Hong Lu. MiR-361-3p inhibits β-amyloid accumulation and attenuates cognitive deficits through targeting BACE1 in Alzheimer's disease[J]. Journal of Integrative Neuroscience, 2019, 18(3): 285-291.
[11] Chunlei Liu, Jinju Fang, Wenke Liu. Superoxide dismutase coding of gene polymorphisms associated with susceptibility to Parkinson’s disease[J]. Journal of Integrative Neuroscience, 2019, 18(3): 299-303.
[12] Zhifeng Tian, Xiaoling Zhang, Zhijun Zhao, Fuhua Zhang, Tongxing Deng. The Wnt/β-catenin signaling pathway affects the distribution of cytoskeletal proteins in Aβ treated PC12 cells[J]. Journal of Integrative Neuroscience, 2019, 18(3): 309-312.
[13] Michael G. Z. Ghali. Mechanisms contributing to the genesis of hypoglossal preinspiratory discharge[J]. Journal of Integrative Neuroscience, 2019, 18(3): 313-325.
[14] Ye Zhu, Le Peng, Jian Hu, Yan Chen, Faxiu Chen. Current anti-Alzheimer’s disease effect of natural products and their principal targets[J]. Journal of Integrative Neuroscience, 2019, 18(3): 327-339.
[15] Dapeng Zhu, Caixing Sun, Xiang Qian. MST1 suppresses viability and promotes apoptosis of glioma cells via upregulating SIRT6 expression[J]. Journal of Integrative Neuroscience, 2019, 18(2): 117-126.
No Suggested Reading articles found!