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Vagnozzi AN, Li JG, Chiu J, et al. VPS35 regulates tau phosphorylation and neuropathology in tauopathy. Mol Psychiatry. 2019;doi: 10.1038/s41380-019-0453-x.
Vagnozzi, A. N., Li, J. G., Chiu, J., Razmpour, R., Warfield, R., Ramirez, S. H., & Praticò, D. (2019). VPS35 regulates tau phosphorylation and neuropathology in tauopathy. Molecular psychiatry, . https://doi.org/10.1038/s41380-019-0453-x
Vagnozzi, Alana N, et al. "VPS35 regulates tau phosphorylation and neuropathology in tauopathy." Molecular psychiatry vol. (2019). doi: https://doi.org/10.1038/s41380-019-0453-x
Vagnozzi AN, Li JG, Chiu J, Razmpour R, Warfield R, Ramirez SH, Praticò D. VPS35 regulates tau phosphorylation and neuropathology in tauopathy. Mol Psychiatry. 2019 Jul 09; doi: 10.1038/s41380-019-0453-x. Epub 2019 Jul 09. PMID: 31289348; PMCID: PMC6949432.
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Mol Psychiatry. 2019 Jul 09; doi: 10.1038/s41380-019-0453-x. Epub 2019 Jul 09.

VPS35 regulates tau phosphorylation and neuropathology in tauopathy.

Molecular psychiatry

Alana N Vagnozzi, Jian-Guo Li, Jin Chiu, Roshanak Razmpour, Rebecca Warfield, Servio H Ramirez, Domenico Praticò

Affiliations

  1. Alzheimer's Center at Temple, Department of Pharmacology, Philadelphia, PA, 19140, USA.
  2. Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
  3. Alzheimer's Center at Temple, Department of Pharmacology, Philadelphia, PA, 19140, USA. [email protected].

PMID: 31289348 PMCID: PMC6949432 DOI: 10.1038/s41380-019-0453-x

Abstract

The vacuolar protein sorting 35 (VPS35) is a major component of the retromer recognition core complex which regulates intracellular protein sorting and trafficking. Deficiency in VPS35 by altering APP/Aβ metabolism has been linked to late-onset Alzheimer's disease. Here we report that VPS35 is significantly reduced in Progressive Supra-nuclear Palsy and Picks' disease, two distinct primary tauopathies. In vitro studies show that overexpression of VPS35 leads to a reduction of pathological tau in neuronal cells, whereas genetic silencing of VPS35 results in its accumulation. Mechanistically the availability of active cathepsin D mediates the effect of VPS35 on pathological tau accumulation. Moreover, in a relevant transgenic mouse model of tauopathy, down-regulation of VPS35 results in an exacerbation of motor and learning impairments as well as accumulation of pathological tau and loss of synaptic integrity. Taken together, our data identify VPS35 as a novel critical player in tau metabolism and neuropathology, and a new therapeutic target for human tauopathies.

References

  1. Eur J Cell Biol. 2015 Nov;94(11):513-21 - PubMed
  2. Mol Cell Biol. 2007 Oct;27(19):6842-51 - PubMed
  3. Nat Chem Biol. 2014 Jun;10(6):443-9 - PubMed
  4. Mol Neurodegener. 2012 Jan 05;7(1):1 - PubMed
  5. Mol Psychiatry. 2018 Oct 2;: - PubMed
  6. J Neurosci. 2012 Jan 25;32(4):1467-80 - PubMed
  7. Methods. 2001 Dec;25(4):402-8 - PubMed
  8. Sci Transl Med. 2016 May 11;8(338):338ra66 - PubMed
  9. Mol Neurobiol. 2019 Feb;56(2):1211-1220 - PubMed
  10. Mol Psychiatry. 2020 Oct;25(10):2630-2640 - PubMed
  11. Proc Natl Acad Sci U S A. 2008 May 20;105(20):7327-32 - PubMed
  12. Neurobiol Aging. 2011 Sep;32(9):1607-14 - PubMed
  13. J Parkinsons Dis. 2017;7(2):219-233 - PubMed
  14. Rev Neurosci. 2017 Nov 27;28(8):861-868 - PubMed
  15. Prog Neurobiol. 2013 Jun;105:49-59 - PubMed
  16. Aging Cell. 2018 Feb;17(1): - PubMed
  17. Neurobiol Dis. 2014 Nov;71:1-13 - PubMed
  18. Biochem Biophys Res Commun. 2010 Dec 10;403(2):167-71 - PubMed
  19. Traffic. 2014 Feb;15(2):230-44 - PubMed
  20. Brain Pathol. 2019 Jan;29(1):63-74 - PubMed
  21. Neurobiol Aging. 2012 Sep;33(9):2231.e15-2231.e30 - PubMed
  22. Transl Psychiatry. 2017 Jan 31;7(1):e1020 - PubMed
  23. J Neural Transm (Vienna). 2005 Apr;112(4):547-55 - PubMed
  24. Development. 2015 Jul 15;142(14):2392-6 - PubMed
  25. Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):E2077-82 - PubMed
  26. Neurobiol Aging. 2017 Apr;52:32-38 - PubMed
  27. Ann Neurol. 2014 Jun;75(6):851-63 - PubMed
  28. Neurobiol Aging. 2014 Nov;35(11):2458-2464 - PubMed
  29. Nat Cell Biol. 2011 Jun;13(6):715-21 - PubMed
  30. Aging Cell. 2015 Dec;14(6):1067-74 - PubMed
  31. Eur J Neurosci. 2008 Mar;27(5):1119-30 - PubMed
  32. Cold Spring Harb Perspect Biol. 2014 Feb 01;6(2): - PubMed
  33. Sci Rep. 2015 Jun 16;5:11086 - PubMed
  34. J Cell Biol. 2011 Nov 28;195(5):765-79 - PubMed
  35. Arch Neurol. 2004 Mar;61(3):378-84 - PubMed
  36. Neuron. 2007 Feb 1;53(3):337-51 - PubMed
  37. Annu Rev Neurosci. 2011;34:185-204 - PubMed
  38. Ann Neurol. 2005 Dec;58(6):909-19 - PubMed
  39. J Neurochem. 1997 Nov;69(5):2026-38 - PubMed
  40. Transl Psychiatry. 2017 Dec 18;7(12):1288 - PubMed
  41. J Cell Biol. 2004 Apr;165(1):111-22 - PubMed

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