CoChat
Sign Up
Cited by 14

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

AAV-Mediated Expression of Dominant-Negative ULK1 Increases Neuronal Survival and Enhances Motor Performance in the MPTP Mouse Model of Parkinson’s Disease

Balke, Dirk, Tatenhorst, Lars, Dambeck, Vivian, Ribas, Vinicius Toledo, Vahsen, Björn F., Michel, Uwe, Bähr, Mathias, Lingor, Paul·2020·Molecular Neurobiology
DOI 10.1007/s12035-019-01744-0
Open this paper in CoChat — free account

Abstract

Loss of nigrostriatal projections by axonal degeneration is a key early event in Parkinson's disease (PD) pathophysiology, being accountable for the lack of dopamine in the nigrostriatal system and resulting in motor symptoms such as bradykinesia, rigidity, and tremor. Since autophagy is an important mechanism contributing to axonal degeneration, we aimed to evaluate the effects of competitive autophagy inhibition in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD in vivo. Adeno-associated viral vector (AAV)-mediated overexpression of a dominant-negative form of the unc-51 like autophagy-initiating kinase (ULK1.DN) in the substantia nigra was induced 3 weeks before MPTP treatment. Analysis of motor behavior demonstrated a significant improvement of ULK1.DN expressing mice after MPTP treatment. Immunohistochemical analyses of dopaminergic nigral neurons and nigrostriatal projections revealed a significant protection from MPTP-induced neurotoxicity after ULK1.DN expression. Western blot analysis linked these findings to an activation of mTOR signaling. Taken together, our results indicate that expression of ULK1.DN can attenuate MPTP-induced axonal neurodegeneration, suggesting that ULK1 could be a promising novel target in the treatment of PD.

Overview

Integrity signals

Registry

Crossref · 10.1007/s12035-019-01744-0

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 2 references

Research works printed but not linked: 51

  1. Salat D, Noyce AJ, Schrag A, Tolosa E (2016) Challenges of modifying disease progression in prediagnostic Parkinson’s disease. Lancet Neurol 15:637–648. https://doi.org/10.1016/S1474-4422(16)00060-0 · DOI
  2. Burke RE, O’Malley K (2013) Axon degeneration in Parkinson’s disease. Exp Neurol 246:72–83. https://doi.org/10.1016/j.expneurol.2012.01.011 · DOI
  3. Lingor P, Koch JC, Tönges L, Bähr M (2012) Axonal degeneration as a therapeutic target in the CNS. Cell Tissue Res 349:289–311. https://doi.org/10.1007/s00441-012-1362-3 · DOI · Paper page
  4. Tagliaferro P, Burke RE (2016) Retrograde axonal degeneration in Parkinson disease. J Park Dis 6:1–15. https://doi.org/10.3233/JPD-150769 · DOI · Paper page
  5. Banerjee R, Beal MF, Thomas B (2010) Autophagy in neurodegenerative disorders: Pathogenic roles and therapeutic implications. Trends Neurosci 33:541–549. https://doi.org/10.1016/j.tins.2010.09.001 · DOI · Paper page
  6. Nah J, Yuan J, Jung Y-K (2015) Autophagy in neurodegenerative diseases: from mechanism to therapeutic approach. Mol Cell 38:381–389. https://doi.org/10.14348/molcells.2015.0034 · DOI
  7. Wong E, Cuervo AM (2010) Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13:805–811. https://doi.org/10.1038/nn.2575 · DOI · Paper page
  8. Koch JC, Knöferle J, Tönges L, Ostendorf T, Bähr M, Lingor P (2010) Acute axonal degeneration in vivo is attenuated by inhibition of autophagy in a calcium-dependent manner. Autophagy 6:658–659. https://doi.org/10.4161/auto.6.5.12188 · DOI
  9. Knöferle J, Koch JC, Ostendorf T et al (2010) Mechanisms of acute axonal degeneration in the optic nerve in vivo. Proc Natl Acad Sci U S A 107:6064–6069. https://doi.org/10.1073/pnas.0909794107 · DOI · Paper page
  10. Ribas VT, Schnepf B, Challagundla M, Koch JC, Bähr M, Lingor P (2015) Early and sustained activation of autophagy in degenerating axons after spinal cord injury. Brain Pathol 25:157–170. https://doi.org/10.1111/bpa.12170 · DOI · Paper page
  11. Cheng H-C, Kim SR, Oo TF, Kareva T, Yarygina O, Rzhetskaya M, Wang C, During M et al (2011) Akt suppresses retrograde degeneration of dopaminergic axons by inhibition of macroautophagy. J Neurosci 31:2125–2135. https://doi.org/10.1523/JNEUROSCI.5519-10.2011 · DOI
  12. Dagda RK, Das BT, Janda E (2013) How parkinsonian toxins dysregulate the autophagy machinery. Int J Mol Sci 14:22163–22189. https://doi.org/10.3390/ijms141122163 · DOI
  13. Janda E, Isidoro C, Carresi C, Mollace V (2012) Defective autophagy in Parkinson’s disease: Role of oxidative stress. Mol Neurobiol 46:639–661. https://doi.org/10.1007/s12035-012-8318-1 · DOI
  14. Murphy KE, Gysbers AM, Abbott SK, Spiro AS, Furuta A, Cooper A, Garner B, Kabuta T et al (2015) Lysosomal-associated membrane protein 2 isoforms are differentially affected in early Parkinson’s disease. Mov Disord 30:1639–1647. https://doi.org/10.1002/mds.26141 · DOI
  15. Zhang L, Dong Y, Xu X, Xu Z (2012) The role of autophagy in Parkinson’s disease. Neural Regen Res 7:141–145. https://doi.org/10.3969/j.issn.1673-5374.2012.02.011 · DOI
  16. Kaur J, Debnath J (2015) Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol 16:461–472. https://doi.org/10.1038/nrm4024 · DOI
  17. Chan EYW, Longatti A, McKnight NC, Tooze SA (2009) Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol 29:157–171. https://doi.org/10.1128/MCB.01082-08 · DOI · Paper page
  18. Zolotukhin S, Byrne BJ, Mason E, Zolotukhin I, Potter M, Chesnut K, Summerford C, Samulski RJ et al (1999) Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther 6:973–985. https://doi.org/10.1038/sj.gt.3300938 · DOI
  19. Zhong L, Li B, Mah CS, Govindasamy L, Agbandje-McKenna M, Cooper M, Herzog RW, Zolotukhin I et al (2008) Next generation of adeno-associated virus 2 vectors: Point mutations in tyrosines lead to high-efficiency transduction at lower doses. Proc Natl Acad Sci 105:7827–7832. https://doi.org/10.1073/pnas.0802866105 · DOI · Paper page
  20. Tatenhorst L, Tönges L, Saal K-A, Koch JC, Szegő ÉM, Bähr M, Lingor P (2014) Rho kinase inhibition by fasudil in the striatal 6-hydroxydopamine lesion mouse model of Parkinson disease. J Neuropathol Exp Neurol 73:770–779. https://doi.org/10.1097/NEN.0000000000000095 · DOI
  21. Saal K-A, Koch JC, Tatenhorst L, Szegő ÉM, Ribas VT, Michel U, Bähr M, Tönges L et al (2015) AAV.shRNA-mediated downregulation of ROCK2 attenuates degeneration of dopaminergic neurons in toxin-induced models of Parkinson’s disease in vitro and in vivo. Neurobiol Dis 73:150–162. https://doi.org/10.1016/j.nbd.2014.09.013 · DOI
  22. Tönges L, Frank T, Tatenhorst L et al (2012) Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson’s disease. Brain 135:3355–3370. https://doi.org/10.1093/brain/aws254 · DOI · Paper page
  23. Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST (2000) CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 39:777–787 · DOI
  24. Tatenhorst L, Eckermann K, Dambeck V, Fonseca-Ornelas L, Walle H, Lopes da Fonseca T, Koch JC, Becker S et al (2016) Fasudil attenuates aggregation of α-synuclein in models of Parkinson’s disease. Acta Neuropathol Commun 4:39. https://doi.org/10.1186/s40478-016-0310-y · DOI · Paper page
  25. Bhimani AD, Kheirkhah P, Arnone GD, Nahhas CR, Kumar P, Wonais M, Hidrogo H, Aguilar E et al (2017) Functional gait analysis in a spinal contusion rat model. Neurosci Biobehav Rev 83:540–546. https://doi.org/10.1016/j.neubiorev.2017.09.007 · DOI
  26. Kim J, Kundu M, Viollet B, Guan K-L (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13:132–141. https://doi.org/10.1038/ncb2152 · DOI · Paper page
  27. Zhu J-H, Guo F, Shelburne J et al (2003) Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases. Brain Pathol 13:473–481 · DOI
  28. Beilina A, Cookson MR (2016) Genes associated with Parkinson’s disease: Regulation of autophagy and beyond. J Neurochem 139:91–107. https://doi.org/10.1111/jnc.13266 · DOI
  29. Kurowska Z, Kordower JH, Stoessl AJ, Burke RE, Brundin P, Yue Z, Brady ST, Milbrandt J et al (2016) Is axonal degeneration a key early event in Parkinson’s disease? J Park Dis 6:703–707. https://doi.org/10.3233/JPD-160881 · DOI
  30. Ribas VT, Koch JC, Michel U, Bähr M, Lingor P (2016) Attenuation of axonal degeneration by Calcium Channel inhibitors improves retinal ganglion cell survival and regeneration after optic nerve crush. Mol Neurobiol 54:72–86. https://doi.org/10.1007/s12035-015-9676-2 · DOI
  31. Zhang J-N, Michel U, Lenz C, Friedel CC, Köster S, d’Hedouville Z, Tönges L, Urlaub H et al (2016) Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration. Sci Rep 6:37050. https://doi.org/10.1038/srep37050 · DOI
  32. Miki Y, Tanji K, Mori F, Utsumi J, Sasaki H, Kakita A, Takahashi H, Wakabayashi K (2016) Alteration of upstream autophagy-related proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy body disease. Brain Pathol 26:359–370. https://doi.org/10.1111/bpa.12297 · DOI
  33. Miki Y, Shimoyama S, Kon T, Ueno T, Hayakari R, Tanji K, Matsumiya T, Tsushima E et al (2018) Alteration of autophagy-related proteins in peripheral blood mononuclear cells of patients with Parkinson’s disease. Neurobiol Aging 63:33–43. https://doi.org/10.1016/j.neurobiolaging.2017.11.006 · DOI
  34. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909 · DOI · Paper page
  35. Przedborski S, Jackson-Lewis V, Naini AB, Jakowec M, Petzinger G, Miller R, Akram M (2001) The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 76:1265–1274 · DOI
  36. Huang D, Xu J, Wang J, Tong J, Bai X, Li H, Wang Z, Huang Y et al (2017) Dynamic changes in the nigrostriatal pathway in the MPTP mouse model of Parkinson’s disease. Parkinsons Dis 2017:1–7. https://doi.org/10.1155/2017/9349487 · DOI
  37. Rommelfanger KS (2011) Extrastriatal dopaminergic circuits of the basal ganglia. Front Neuroanat 4:1–17. https://doi.org/10.3389/fnana.2010.00139 · DOI
  38. Pilotto A, di Cola FS, Premi E et al (2019) Extrastriatal dopaminergic and serotonergic pathways in Parkinson’s disease and in dementia with Lewy bodies: a 123I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging 46:1642–1651. https://doi.org/10.1007/s00259-019-04324-5 · DOI
  39. Chan EYW, Kir S, Tooze SA (2007) siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy. J Biol Chem 282:25464–25474. https://doi.org/10.1074/jbc.M703663200 · DOI · Paper page
  40. Alers S, Loffler a. S, Wesselborg S, Stork B (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 32:2–11. https://doi.org/10.1128/MCB.06159-11 · DOI · Paper page
  41. Toda H, Mochizuki H, Flores R, Josowitz R, Krasieva TB, LaMorte VJ, Suzuki E, Gindhart JG et al (2008) UNC-51/ATG1 kinase regulates axonal transport by mediating motor-cargo assembly. Genes Dev 22:3292–3307. https://doi.org/10.1101/gad.1734608 · DOI
  42. Chu CT, Zhu J, Dagda R (2007) Beclin 1-independent pathway of damage-induced mitophagy and autophagic stress: implications for neurodegeneration and cell death. Autophagy 3:663–666 · DOI
  43. Zhang H, Duan C, Yang H (2015) Defective autophagy in Parkinson’s disease: Lessons from genetics. Mol Neurobiol 51:89–104. https://doi.org/10.1007/s12035-014-8787-5 · DOI
  44. Li Y, Zhang J, Yang C (2015) UNC-51-like kinase 1 blocks S6k1 phosphorylation contributes to neurodegeneration in Parkinson’s disease model in vitro. Biochem Biophys Res Commun 459:196–200. https://doi.org/10.1016/j.bbrc.2015.02.008 · DOI
  45. Lee S-B, Kim H-T, Yang HO, Jang W (2018) Anodal transcranial direct current stimulation prevents methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by modulating autophagy in an in vivo mouse model of Parkinson’s disease. Sci Rep 8:15165. https://doi.org/10.1038/s41598-018-33515-7 · DOI
  46. Wen Z, Zhang J, Tang P, Tu N, Wang K, Wu G (2018) Overexpression of miR-185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson’s disease. Mol Med Rep 17:131–137. https://doi.org/10.3892/mmr.2017.7897 · DOI
  47. Jang Y chul, Hwang DJ, Koo JH, et al (2018) Association of exercise-induced autophagy upregulation and apoptosis suppression with neuroprotection against pharmacologically induced Parkinson’s disease. J Exerc Nutr Biochem 22:1–8. https://doi.org/10.20463/jenb.2018.0001 · DOI
  48. Ouyang L, Zhang L, Zhang S, Yao D, Zhao Y, Wang G, Fu L, Lei P et al (2018) Small-molecule activator of UNC-51-like kinase 1 (ULK1) that induces cytoprotective autophagy for Parkinson’s disease treatment. J Med Chem 61:2776–2792. https://doi.org/10.1021/acs.jmedchem.7b01575 · DOI
  49. Pupyshev AB, Tikhonova MA, Akopyan AA, Tenditnik MV, Dubrovina NI, Korolenko TA (2019) Therapeutic activation of autophagy by combined treatment with rapamycin and trehalose in a mouse MPTP-induced model of Parkinson’s disease. Pharmacol Biochem Behav 177:1–11. https://doi.org/10.1016/j.pbb.2018.12.005 · DOI
  50. Tang F, Hu P, Yang Z, Xue C, Gong J, Sun S, Shi L, Zhang S et al (2017) SBI0206965, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell growth by modulating both autophagy and apoptosis pathways. Oncol Rep 37:3449–3458. https://doi.org/10.3892/or.2017.5635 · DOI
  51. Egan DF, Chun MGH, Vamos M, Zou H, Rong J, Miller CJ, Lou HJ, Raveendra-Panickar D et al (2015) Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol Cell 59:285–297. https://doi.org/10.1016/j.molcel.2015.05.031 · DOI · Paper page

Cited by

Sorted by citations

See all 14

Metadata

Authors
Balke, D., Tatenhorst, L., Dambeck, V., Ribas, V. T., Vahsen, B. F., Michel, U., Bähr, M., & Lingor, P.
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2019-08-24
Volume
57
Issue
2
Pages
685-697
ISSN
  • 0893-7648
  • 1559-1182
DOI
10.1007/s12035-019-01744-0
Cited by
14
References
2
Language
en
Licence
Funders
  • Department of Neurology, University Medical Center Göttingen (-)
  • National Council for Scientific and Technological Development (CNPq), Brazil (-)
  • Cluster of Excellence and DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen (-)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review