Advertisement

Twist1 Plays an Anti-apoptotic Role in Mutant Huntingtin Expression Striatal Progenitor Cells

  • Wei-Ping Jen
  • Hui-Mei Chen
  • Yow-Sien Lin
  • Yijuang Chern
  • Yi-Ching LeeEmail author
Article

Abstract

The Twist basic helix-loop-helix transcription factor 1 (Twist1) has been implicated in embryogenesis and carcinogenesis, due to its effects on cell proliferation and anti-apoptosis signaling. Interestingly, a connection between Twist1 and neurotoxicity was recently made in mutant huntingtin (mHtt)-expressing primary cortical neurons; however, the role of Twist1 in Huntington’s disease (HD)-affected striatal neurons remains undescribed. In this study, we evaluated the expression and function of Twist1 in the R6/2 HD mouse model, which expresses the polyQ-expanded N-terminal portion of human HTT protein, and a pair of striatal progenitor cell lines (STHdhQ109 and STHdhQ7), which express polyQ-expanded or non-expanded full-length mouse Htt. We further probed upstream signaling events and Twist1 anti-apoptotic function in the striatal progenitor cell lines. Twist1 was increased in mHtt-expressing striatal progenitor cells (STHdhQ109) and was correlated with disease progression in striatum and cortex brain regions of R6/2 mice. In the cell model, downregulation of Twist1 induced death of STHdhQ109 cells but had no effect on wild-type striatal progenitor cells (STHdhQ7). Twist1 knockdown stimulated caspase-3 activation and apoptosis. Furthermore, we found that signal transducer and activator of transcription 3 (STAT3) were increased in HD striatal progenitor cells and acted as an upstream regulator of Twist1. As such, inhibition of STAT3 induced apoptosis in HD striatal progenitor cells. Our results suggest that mHtt upregulates STAT3 to induce Twist1 expression. Upregulated Twist1 inhibits apoptosis, which may protect striatal cells from death during disease progression. Thus, we propose that Twist1 might play a protective role against striatal degeneration in HD.

Keywords

Twist1 Huntington’s disease Apoptosis Neuroprotection STAT3 

Abbreviations

ANOVA

Analysis of variance

BAT

Brown adipose tissue

Bad

Bcl-2-associated death promoter

Bcl-2

B cell lymphoma 2

Bdnf

Brain-derived neurotrophic factor

BSA

Bovine serum albumin

CA1

Hippocampal Cornu Ammonis area 1

CASP3

Caspase-3

CB1R

Cannabinoid receptor type 1 receptor

cCASP3

Cleaved caspase-3

(c)DNA

Complementary DNA

CFP

Cyan fluorescent protein

CNS

Central nervous system

DMEM

Dulbecco’s modified Eagle medium

DMF

Dimethylformamide

EMT

Epithelial-mesenchymal transition

H3K4me3

Histone 3 lysine 4 trimethylation

HD

Huntington’s disease

HIFs

Hypoxia-inducible factors

hrGFP

Humanized recombinant green fluorescent protein

Htt

Huntingtin

IR

Insulin resistant

mHtt

Mutant huntingtin

MTT

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

PBS

Phosphate-buffered saline

PCR

Polymerase chain reaction

PGC-1α

PPAR gamma coactivator 1-alpha

PI

Propidium iodide

PNS

Peripheral nervous system

PolyQ

Polyglutamine

PPAR

Peroxisome proliferator-activated receptor

pSTAT3

Phosphorylated form of STAT3

RT-qPCR

Real-time quantitative qPCR

STAT3

Signal transducer and activator of transcription 3

SDS

Sodium dodecyl sulfate

SDS-PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

STHdhQ109

Mutant huntingtin striatal progenitor cells

STHdhQ7

Wild-type striatal progenitor cells

Twist1

Twist basic helix-loop-helix transcription factor 1

TF

Transcription factor

TNF-α

Tumor necrosis factor alpha

TrkB

Tropomyosin receptor kinase B

VCP

Valosin-containing protein

WB

Western blot

WT

Wild-type

Notes

Acknowledgments

We are grateful to Dr. Elena Cattaneo (University of Milano, Italy) for providing the striatal cell lines (STHdhQ7, and STHdhQ109). We thank Dr. Kou-Juey Wu (Chang Gung Memorial Hospital, Taiwan) for providing the sh1-Ctrl and sh1-Twist1 constructs. We thank Ms. Shu-Chen Shen (Advanced Optical Microscope Core Facility, Scientific Instrument Center of Academia Sinica) for the technical assistance of confocal microscopy. We also thank Ms. Chia-Chen Dai and Tzu-Wen Tai (Flow Cytometry Core Facility of the Institute of Biomedical Sciences, Academia Sinica) for the technical support with cell sorting. We are also grateful to the RNAi Core Facility (Academia Sinica) and DNA Sequencing Core Facility (IBMS, Academia Sinica) for their help. We also thank Dr. Marcus J. Calkins for reading and editing the manuscript.

Authors’ Contributions

WPJ conceived research, designed experiments, performed and analyzed real-time qPCR, immunofluorescence staining, IHC, western blotting (except brain nuclear-cytosolic fractionation results), cell culture and preparation, cell survival assay, and annexin V/PI apoptosis analysis, Seahorse Mito Stress assay, and wrote the manuscript. HMC maintained the mice used in this study. YSL carried out nuclear-cytosolic fractionation results. YCL and YC refined the experimental design and edited the manuscript. All authors read and approved the final manuscript.

Funding Information

This work was supported by grants from the Ministry of Science and Technology (NSC97-2321-B-001-030, NSC98-2321-B-001-017, NSC99-2321-B-001-012, NSC100-2321-B-001-00, 104-2321-B-001-063) and Academia Sinica (AS-100-TP2-B02), Taiwan.

Compliance with Ethical Standards

Animal experiments were performed in accordance with the protocols approved by the Academia Sinica Institutional Animal Care and Utilization Committee.

Competing Interests

The authors declare that they have no competing interests.

Supplementary material

12035_2019_1836_MOESM1_ESM.pdf (14.3 mb)
ESM 1 (PDF 14629 kb)

References

  1. 1.
    Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y et al (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87(3):493–506CrossRefGoogle Scholar
  2. 2.
    Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington’s disease. European Journal of Neuroscience 27(11):2803–2820.  https://doi.org/10.1111/j.1460-9568.2008.06310.x CrossRefPubMedGoogle Scholar
  3. 3.
    Hickey MA, Chesselet M-F (2003) Apoptosis in Huntington’s disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry 27(2):255–265.  https://doi.org/10.1016/S0278-5846(03)00021-6 CrossRefPubMedGoogle Scholar
  4. 4.
    Saudou F, Finkbeiner S, Devys D, Greenberg ME Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95(1):55–66.  https://doi.org/10.1016/S0092-8674(00)81782-1 CrossRefGoogle Scholar
  5. 5.
    Castanon I, Baylies MK (2002) A Twist in fate: evolutionary comparison of Twist structure and function. Gene 287(1-2):11–22CrossRefGoogle Scholar
  6. 6.
    Qin Q, Xu Y, He T, Qin C, Xu J (2012) Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell research 22(1):90–106.  https://doi.org/10.1038/cr.2011.144 CrossRefPubMedGoogle Scholar
  7. 7.
    Ang S-L, Rossant J (1994) HNF-3β is essential for node and notochord formation in mouse development. Cell 78(4):561–574.  https://doi.org/10.1016/0092-8674(94)90522-3 CrossRefPubMedGoogle Scholar
  8. 8.
    Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Developmental cell 14(6):818–829.  https://doi.org/10.1016/j.devcel.2008.05.009 CrossRefPubMedGoogle Scholar
  9. 9.
    Chen ZF, Behringer RR (1995) twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev 9(6):686–699CrossRefGoogle Scholar
  10. 10.
    Maestro R, Dei Tos AP, Hamamori Y, Krasnokutsky S, Sartorelli V, Kedes L, Doglioni C, Beach DH et al (1999) Twist is a potential oncogene that inhibits apoptosis. Genes & development 13(17):2207–2217CrossRefGoogle Scholar
  11. 11.
    Qian J, Luo Y, Gu X, Zhan W, Wang X (2013) Twist1 promotes gastric cancer cell proliferation through up-regulation of FoxM1. PLoS ONE 8(10):e77625.  https://doi.org/10.1371/journal.pone.0077625 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kulaberoglu Y, Gundogdu R, Hergovich A (2016) Chapter 15 - the role of p53/p21/p16 in DNA-damage signaling and DNA repair. In: Kovalchuk I, Kovalchuk O (eds) Genome Stability. Academic Press, Boston, pp. 243–256.  https://doi.org/10.1016/B978-0-12-803309-8.00015-X CrossRefGoogle Scholar
  13. 13.
    Banin S, Moyal L, Shieh SY, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C et al (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281(5383):1674–1677.  https://doi.org/10.1126/science.281.5383.1674 CrossRefPubMedGoogle Scholar
  14. 14.
    Valsesia-Wittmann S, Magdeleine M, Dupasquier S, Garin E, Jallas A-C, Combaret V, Krause A, Leissner P et al (2004) Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer cell 6(6):625–630.  https://doi.org/10.1016/j.ccr.2004.09.033 CrossRefPubMedGoogle Scholar
  15. 15.
    Shiota M, Izumi H, Onitsuka T, Miyamoto N, Kashiwagi E, Kidani A, Hirano G, Takahashi M et al (2008) Twist and p53 reciprocally regulate target genes via direct interaction. Oncogene 27:5543–5553.  https://doi.org/10.1038/onc.2008.176 CrossRefPubMedGoogle Scholar
  16. 16.
    Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (1999) Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A. Cell 96(3):405–413CrossRefGoogle Scholar
  17. 17.
    Ansieau S, Morel AP, Hinkal G, Bastid J, Puisieux A (2010) TWISTing an embryonic transcription factor into an oncoprotein. Oncogene 29:3173–3184.  https://doi.org/10.1038/onc.2010.92 CrossRefPubMedGoogle Scholar
  18. 18.
    Cheng GZ, Zhang W, Sun M, Wang Q, Coppola D, Mansour M, Xu L, Costanzo C et al (2008) Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. Journal of Biological Chemistry 283(21):14665–14673.  https://doi.org/10.1074/jbc.M707429200 CrossRefPubMedGoogle Scholar
  19. 19.
    Šošić D, Richardson JA, Yu K, Ornitz DM, Olson EN (2003) Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB Activity. Cell 112(2):169–180.  https://doi.org/10.1016/S0092-8674(03)00002-3 CrossRefPubMedGoogle Scholar
  20. 20.
    Hsiao H-Y, Chen Y-C, Chen H-M, Tu P-H, Chern Y (2013) A critical role of astrocyte-mediated nuclear factor-κB-dependent inflammation in Huntington’s disease. Human molecular genetics 22(9):1826–1842.  https://doi.org/10.1093/hmg/ddt036 CrossRefPubMedGoogle Scholar
  21. 21.
    Ben Haim L, Ceyzeriat K, Carrillo-de Sauvage MA, Aubry F, Auregan G, Guillermier M, Ruiz M, Petit F et al (2015) The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer’s and Huntington’s diseases. The Journal of neuroscience : the official journal of the Society for Neuroscience 35(6):2817–2829.  https://doi.org/10.1523/JNEUROSCI.3516-14.2015 CrossRefGoogle Scholar
  22. 22.
    Pan Y, Zhu Y, Yang W, Tycksen E, Liu S, Palucki J, Zhu L, Sasaki Y et al (2018) The role of Twist1 in mutant huntingtin-induced transcriptional alterations and neurotoxicity. The Journal of biological chemistry 293(30):11850–11866.  https://doi.org/10.1074/jbc.RA117.001211 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Vichalkovski A, Gresko E, Hess D, Restuccia DF, Hemmings BA (2010) PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage. Oncogene 29(24):3554–3565. http://www.nature.com/onc/journal/v29/n24/suppinfo/onc2010115s1.html CrossRefGoogle Scholar
  24. 24.
    Lu S, Yu L, Mu Y, Ma J, Tian J, Xu WEI, Wang H (2014) Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells. Molecular Medicine Reports 10(1):53–60.  https://doi.org/10.3892/mmr.2014.2212 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ferrante RJ, Kowall NW, Beal MF, Richardson EP, Bird ED, Martin JB (1985) Selective sparing of a class of striatal neurons in Huntington’s disease. Science 230(4725):561–563.  https://doi.org/10.1126/science.2931802 CrossRefPubMedGoogle Scholar
  26. 26.
    Richardson EP Jr, Ferrante RJ, Vonsattel J-P, Stevens TJ, Bird ED, Myers RH (1985) Neuropathological classification of Huntington’s disease. Journal of Neuropathology & Experimental Neurology 44(6):559–577.  https://doi.org/10.1097/00005072-198511000-00003 CrossRefGoogle Scholar
  27. 27.
    Morigaki R, Goto S (2017) Striatal vulnerability in Huntington’s disease: neuroprotection versus neurotoxicity. Brain sciences 7(6):63.  https://doi.org/10.3390/brainsci7060063 CrossRefPubMedCentralGoogle Scholar
  28. 28.
    Lin YS, Cheng TH, Chang CP, Chen HM, Chern Y (2013) Enhancement of brain-type creatine kinase activity ameliorates neuronal deficits in Huntington’s disease. Biochimica et biophysica acta 1832(6):742–753.  https://doi.org/10.1016/j.bbadis.2013.02.006 CrossRefPubMedGoogle Scholar
  29. 29.
    Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, Huang CH, Kao SY et al (2010) Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nature cell biology 12(10):982–992.  https://doi.org/10.1038/ncb2099 CrossRefPubMedGoogle Scholar
  30. 30.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685CrossRefGoogle Scholar
  31. 31.
    Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunological Methods 119(2):203–210CrossRefGoogle Scholar
  32. 32.
    Vonsattel JP, DiFiglia M (1998) Huntington disease. Journal of neuropathology and experimental neurology 57(5):369–384CrossRefGoogle Scholar
  33. 33.
    Schutte B, Nuydens R, Geerts H, Ramaekers F (1998) Annexin V binding assay as a tool to measure apoptosis in differentiated neuronal cells. Journal of Neuroscience Methods 86(1):63–69.  https://doi.org/10.1016/S0165-0270(98)00147-2 CrossRefPubMedGoogle Scholar
  34. 34.
    Jacobsen MD, Weil M, Raff MC (1996) Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death. The Journal of Cell Biology 133(5):1041–1051CrossRefGoogle Scholar
  35. 35.
    Leibinger M, Andreadaki A, Diekmann H, Fischer D (2013) Neuronal STAT3 activation is essential for CNTF- and inflammatory stimulation-induced CNS axon regeneration. Cell Death &Amp; Disease 4:e805.  https://doi.org/10.1038/cddis.2013.310 CrossRefGoogle Scholar
  36. 36.
    Mehta ST, Luo X, Park KK, Bixby JL, Lemmon VP (2016) Hyperactivated Stat3 boosts axon regeneration in the CNS. Experimental Neurology 280:115–120.  https://doi.org/10.1016/j.expneurol.2016.03.004 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Zhao J, Li G, Zhang Y, Su X, Hang C (2011) The potential role of JAK2/STAT3 pathway on the anti-apoptotic effect of recombinant human erythropoietin (rhEPO) after experimental traumatic brain injury of rats. Cytokine 56(2):343–350.  https://doi.org/10.1016/j.cyto.2011.07.018 CrossRefPubMedGoogle Scholar
  38. 38.
    Träger U, Magnusson A, Swales NL, Wild E, North J, Lowdell M, Björkqvist M (2013) JAK/STAT signalling in Huntington’s disease immune cells. PLOS Currents Huntington Disease.  https://doi.org/10.1371/currents.hd.5791c897b5c3bebeed93b1d1da0c0648
  39. 39.
    Gitelman I (1997) Twist protein in mouse embryogenesis. Developmental Biology 189(2):205–214.  https://doi.org/10.1006/dbio.1997.8614 CrossRefPubMedGoogle Scholar
  40. 40.
    El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, Jd G, Bonaventure J (2000) Saethre–Chotzen mutations cause TWIST protein degradation or impaired nuclear location. Human Molecular Genetics 9(5):813–819.  https://doi.org/10.1093/hmg/9.5.813 CrossRefPubMedGoogle Scholar
  41. 41.
    Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, Slunt HH, Ratovitski T et al (1999) Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Human molecular genetics 8(3):397–407CrossRefGoogle Scholar
  42. 42.
    Zhang X, Wang Q, Ling MT, Wong YC, Leung SC, Wang X (2007) Anti-apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells. International Journal of Cancer Journal International du Cancer 120(9):1891–1898.  https://doi.org/10.1002/ijc.22489 CrossRefPubMedGoogle Scholar
  43. 43.
    Wallerand H, Robert G, Pasticier G, Ravaud A, Ballanger P, Reiter RE, Ferriere JM (2010) The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers. Urologic oncology 28(5):473–479.  https://doi.org/10.1016/j.urolonc.2008.12.018 CrossRefPubMedGoogle Scholar
  44. 44.
    Feng MY, Wang K, Song HT, Yu HW, Qin Y, Shi QT, Geng JS (2009) Metastasis-induction and apoptosis-protection by TWIST in gastric cancer cells. Clinical & experimental metastasis 26(8):1013–1023.  https://doi.org/10.1007/s10585-009-9291-6 CrossRefGoogle Scholar
  45. 45.
    Baydyuk M, Xu B (2014) BDNF signaling and survival of striatal neurons. Front Cell Neurosci 8:254–254.  https://doi.org/10.3389/fncel.2014.00254 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Gines S, Paoletti P, Alberch J (2010) Impaired TrkB-mediated ERK1/2 activation in Huntington disease knock-in striatal cells involves reduced p52/p46 Shc expression. The Journal of biological chemistry 285:21537–21548.  https://doi.org/10.1074/jbc.M109.084202 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lu J, Tan M, Cai Q (2015) The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Letters 356(2, Part A):156–164.  https://doi.org/10.1016/j.canlet.2014.04.001 CrossRefPubMedGoogle Scholar
  48. 48.
    Ruckenstuhl C, Büttner S, Carmona-Gutierrez D, Eisenberg T, Kroemer G, Sigrist SJ, Fröhlich K-U, Madeo F (2009) The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer. PLOS ONE 4(2):e4592.  https://doi.org/10.1371/journal.pone.0004592 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029–1033.  https://doi.org/10.1126/science.1160809 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Tran Q, Lee H, Park J, Kim S-H, Park J (2016) Targeting cancer metabolism - revisiting the Warburg effects. Toxicological research 32(3):177–193.  https://doi.org/10.5487/TR.2016.32.3.177 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Pan D, Fujimoto M, Lopes A, Wang YX (2009) Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell 137(1):73–86.  https://doi.org/10.1016/j.cell.2009.01.051 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Lu S, Wang H, Ren R, Shi X, Zhang Y, Ma W (2018) Reduced expression of Twist 1 is protective against insulin resistance of adipocytes and involves mitochondrial dysfunction. Scientific Reports 8(1):12590.  https://doi.org/10.1038/s41598-018-30820-z CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Johri A, Chandra A, Beal MF (2013) PGC-1alpha, mitochondrial dysfunction, and Huntington’s disease. Free radical biology & medicine 62:37–46.  https://doi.org/10.1016/j.freeradbiomed.2013.04.016 CrossRefGoogle Scholar
  54. 54.
    Mochel F, Haller RG (2011) Energy deficit in Huntington disease: why it matters. The Journal of Clinical Investigation 121(2):493–499.  https://doi.org/10.1172/JCI45691 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Dickey AS, Pineda VV, Tsunemi T, Liu PP, Miranda HC, Gilmore-Hall SK, Lomas N, Sampat KR et al (2015) PPAR-δ is repressed in Huntington’s disease, is required for normal neuronal function and can be targeted therapeutically. Nature Medicine 22:37.  https://doi.org/10.1038/nm.4003 https://www.nature.com/articles/nm.4003#supplementary-information CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Sameni S, Syed A, Marsh JL, Digman MA (2016) The phasor-FLIM fingerprints reveal shifts from OXPHOS to enhanced glycolysis in Huntington disease. Scientific Reports 6:34755.  https://doi.org/10.1038/srep34755 https://www.nature.com/articles/srep34755#supplementary-information CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Vallee A, Lecarpentier Y, Guillevin R, Vallee JN (2018) Aerobic glycolysis in amyotrophic lateral sclerosis and Huntington’s disease. Rev Neurosci 29(5):547–555.  https://doi.org/10.1515/revneuro-2017-0075 CrossRefPubMedGoogle Scholar
  58. 58.
    Morea V, Bidollari E, Colotti G, Fiorillo A, Rosati J, De Filippis L, Squitieri F, Ilari A (2017) Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure? Amino Acids 49(7):1147–1157.  https://doi.org/10.1007/s00726-017-2417-2 CrossRefPubMedGoogle Scholar
  59. 59.
    Polyzos AA, Lee DY, Datta R, Hauser M, Budworth H, Holt A, Mihalik S, Goldschmidt P et al (2019) Metabolic reprogramming in astrocytes distinguishes region-specific neuronal susceptibility in Huntington mice. Cell Metabolism 29(6):1258–1273.e1211.  https://doi.org/10.1016/j.cmet.2019.03.004 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Floc’h N, Kolodziejski J, Akkari L, Simonin Y, Ansieau S, Puisieux A, Hibner U, Lassus P (2013) Modulation of oxidative stress by Twist oncoproteins. PLoS ONE 8(8):e72490.  https://doi.org/10.1371/journal.pone.0072490 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Kovtun IV, Liu Y, Bjoras M, Klungland A, Wilson SH, McMurray CT (2007) OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 447(7143):447–452.  https://doi.org/10.1038/nature05778 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD (2016) The role of reactive oxygen species in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease: a mini review. Oxidative Medicine and Cellular Longevity 2016:15.  https://doi.org/10.1155/2016/8590578 CrossRefGoogle Scholar
  63. 63.
    Browne SE, Bowling AC, Macgarvey U, Baik MJ, Berger SC, Muquit MMK, Bird ED, Beal MF (2004) Oxidative damage and metabolic dysfunction in Huntington’s disease: selective vulnerability of the basal ganglia. Annals of Neurology 41(5):646–653.  https://doi.org/10.1002/ana.410410514 CrossRefGoogle Scholar
  64. 64.
    Browne SE, Beal MF (2006) Oxidative damage in Huntington’s disease pathogenesis. Antioxidants & redox signaling 8(11-12):2061–2073.  https://doi.org/10.1089/ars.2006.8.2061 CrossRefGoogle Scholar
  65. 65.
    Wyttenbach A, Sauvageot O, Carmichael J, Diaz-Latoud C, Arrigo AP, Rubinsztein DC (2002) Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Human molecular genetics 11(9):1137–1151CrossRefGoogle Scholar
  66. 66.
    Klivenyi P, Ferrante RJ, Gardian G, Browne S, Chabrier P-E, Beal MF (2004) Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington’s disease. Journal of neurochemistry 86(1):267–272.  https://doi.org/10.1046/j.1471-4159.2003.t01-1-01868.x CrossRefGoogle Scholar
  67. 67.
    Stack EC, Matson WR, Ferrante RJ (2008) Evidence of oxidant damage in Huntington’s disease: translational strategies using antioxidants. Annals of the New York Academy of Sciences 1147(1):79–92.  https://doi.org/10.1196/annals.1427.008 CrossRefPubMedGoogle Scholar
  68. 68.
    Túnez I, Sánchez-López F, Agüera E, Fernández-Bolaños R, Sánchez FM, Tasset-Cuevas I (2011) Important role of oxidative stress biomarkers in Huntington’s disease. Journal of Medicinal Chemistry 54(15):5602–5606.  https://doi.org/10.1021/jm200605a CrossRefPubMedGoogle Scholar
  69. 69.
    Damiano M, Diguet E, Malgorn C, D’Aurelio M, Galvan L, Petit F, Benhaim L, Guillermier M et al (2013) A role of mitochondrial complex II defects in genetic models of Huntington’s disease expressing N-terminal fragments of mutant huntingtin. Human molecular genetics 22(19):3869–3882.  https://doi.org/10.1093/hmg/ddt242 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Napoli E, Wong S, Hung C, Ross-Inta C, Bomdica P, Giulivi C (2013) Defective mitochondrial disulfide relay system, altered mitochondrial morphology and function in Huntington’s disease. Human molecular genetics 22(5):989–1004.  https://doi.org/10.1093/hmg/dds503 CrossRefPubMedGoogle Scholar
  71. 71.
    Siddiqui A, Rivera-Sanchez S, Castro Mdel R, Acevedo-Torres K, Rane A, Torres-Ramos CA, Nicholls DG, Andersen JK et al (2012) Mitochondrial DNA damage is associated with reduced mitochondrial bioenergetics in Huntington’s disease. Free Radic Biol Med 53(7):1478–1488.  https://doi.org/10.1016/j.freeradbiomed.2012.06.008 CrossRefPubMedGoogle Scholar
  72. 72.
    Varma H, Cheng R, Voisine C, Hart AC, Stockwell BR (2007) Inhibitors of metabolism rescue cell death in Huntington’s disease models. Proceedings of the National Academy of Sciences 104(36):14525–14530.  https://doi.org/10.1073/pnas.0704482104 CrossRefGoogle Scholar
  73. 73.
    Lin S, Sun L, Lyu X, Ai X, Du D, Su N, Li H, Zhang L et al (2017) Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: a positive metabolic feedback loop. Oncotarget 8(66):110426–110443.  https://doi.org/10.18632/oncotarget.22786 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Kumar A, Ratan RR (2016) Oxidative stress and Huntington’s disease: the good, the bad, and the ugly. Journal of Huntington’s disease 5(3):217–237.  https://doi.org/10.3233/JHD-160205 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Manzanero S, Santro T, Arumugam TV (2013) Neuronal oxidative stress in acute ischemic stroke: sources and contribution to cell injury. Neurochemistry International 62(5):712–718.  https://doi.org/10.1016/j.neuint.2012.11.009 CrossRefPubMedGoogle Scholar
  76. 76.
    Sarafian TA, Montes C, Imura T, Qi J, Coppola G, Geschwind DH, Sofroniew MV (2010) Disruption of astrocyte STAT3 signaling decreases mitochondrial function and increases oxidative stress in vitro. PLOS ONE 5(3):e9532.  https://doi.org/10.1371/journal.pone.0009532 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Guo Z, Jiang H, Xu X, Duan W, Mattson MP (2008) Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization. The Journal of biological chemistry 283(3):1754–1763.  https://doi.org/10.1074/jbc.M703753200 CrossRefPubMedGoogle Scholar
  78. 78.
    Sehara Y, Sawicka K, Hwang J-Y, Latuszek-Barrantes A, Etgen AM, Zukin RS (2013) Survivin is a transcriptional target of STAT3 critical to estradiol neuroprotection in global ischemia. The Journal of Neuroscience 33(30):12364.  https://doi.org/10.1523/JNEUROSCI.1852-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Zhou H, Zhang Z, Wei H, Wang F, Guo F, Gao Z, Marsicano G, Wang Q et al (2013) Activation of STAT3 is involved in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptors in rats. Brain Research 1529:154–164.  https://doi.org/10.1016/j.brainres.2013.07.006 CrossRefPubMedGoogle Scholar
  80. 80.
    Lee N, Neitzel KL, Devlin BK, MacLennan AJ (2004) STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor. Journal of Comparative Neurology 474(4):535–545.  https://doi.org/10.1002/cne.20140 CrossRefPubMedGoogle Scholar
  81. 81.
    Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun H-W et al (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32(5):605–615.  https://doi.org/10.1016/j.immuni.2010.05.003 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715.  https://doi.org/10.1016/j.cell.2008.03.027 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Yang Y, Wang G, Zhu D, Huang Y, Luo Y, Su P, Chen X, Wang Q (2017) Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer. International journal of oncology 51(2):515–524.  https://doi.org/10.3892/ijo.2017.4044 CrossRefPubMedGoogle Scholar
  84. 84.
    Ren H, Du P, Ge Z, Jin Y, Ding D, Liu X, Zou Q (2016) TWIST1 and BMI1 in cancer metastasis and chemoresistance. Journal of Cancer 7(9):1074–1080.  https://doi.org/10.7150/jca.14031 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, Margolick JB, Liotta LA et al (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proceedings of the National Academy of Sciences 104(41):16158CrossRefGoogle Scholar
  86. 86.
    Galoczova M, Coates P, Vojtesek B (2018) STAT3, stem cells, cancer stem cells and p63. Cellular & molecular biology letters 23:12–12.  https://doi.org/10.1186/s11658-018-0078-0 CrossRefGoogle Scholar
  87. 87.
    Curtis MA, Penney EB, Pearson AG, van Roon-Mom WMC, Butterworth NJ, Dragunow M, Connor B, Faull RLM (2003) Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proceedings of the National Academy of Sciences 100(15):9023CrossRefGoogle Scholar
  88. 88.
    de Moura MB, dos Santos LS, Van Houten B (2010) Mitochondrial dysfunction in neurodegenerative diseases and cancer. Environmental and Molecular Mutagenesis 51(5):391–405.  https://doi.org/10.1002/em.20575 CrossRefPubMedGoogle Scholar
  89. 89.
    Driver JA (2012) Understanding the link between cancer and neurodegeneration. Journal of Geriatric Oncology 3(1):58–67.  https://doi.org/10.1016/j.jgo.2011.11.007 CrossRefGoogle Scholar
  90. 90.
    Hernández-Ortega K, Quiroz-Baez R, Arias C (2011) Cell cycle reactivation in mature neurons: a link with brain plasticity, neuronal injury and neurodegenerative diseases? Neuroscience Bulletin 27(3):185–196.  https://doi.org/10.1007/s12264-011-1002-z CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Lanni C, Racchi M, Memo M, Govoni S, Uberti D (2012) p53 at the crossroads between cancer and neurodegeneration. Free Radical Biology and Medicine 52(9):1727–1733.  https://doi.org/10.1016/j.freeradbiomed.2012.02.034 CrossRefPubMedGoogle Scholar
  92. 92.
    Frain L, Swanson D, Cho K, Gagnon D, Lu KP, Betensky RA, Driver J (2017) Association of cancer and Alzheimer’s disease risk in a national cohort of veterans. Alzheimer’s & Dementia 13(12):1364–1370.  https://doi.org/10.1016/j.jalz.2017.04.012 CrossRefGoogle Scholar
  93. 93.
    Vega JN, Dumas J, Newhouse PA (2017) Cognitive effects of chemotherapy and cancer-related treatments in older adults. The American Journal of Geriatric Psychiatry 25(12):1415–1426.  https://doi.org/10.1016/j.jagp.2017.04.001 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Graduate Institute of Life SciencesNational Defense Medical CenterTaipeiTaiwan
  2. 2.Institute of Cellular and Organismic BiologyAcademia SinicaTaipeiTaiwan
  3. 3.Institute of Biomedical SciencesAcademia SinicaTaipeiTaiwan

Personalised recommendations