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The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Pharmacological chaperones stabilize retromer to limit APP processing

Mecozzi, Vincent J, Berman, Diego E, Simoes, Sabrina, Vetanovetz, Chris, Awal, Mehraj R, Patel, Vivek M, Schneider, Remy T, Petsko, Gregory A, Ringe, Dagmar, Small, Scott A·2014·Nature Chemical Biology
DOI 10.1038/nchembio.1508PMC PMC4076047
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Crossref · 10.1038/nchembio.1508

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  • Stabilisation of Retromer expression is neuroprotective.

    “with stabilisation of Retromer expression being neuroprotective [49][50][51][52].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [50]

    The Results report that stabilizing retromer increased retromer protein levels in cultured hippocampal neurons and reduced Aβ accumulation. The Discussion says this may shift APP toward a neuroprotective processing pathway, but the paper does not demonstrate that retromer stabilization itself protects neurons; it presents therapeutic benefit as a possibility for future study. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In vitro, R55 and R33 increased VPS35 and VPS26 protein levels in mouse primary cortical neurons.

    “In vitro, these compounds increased VPS35 and VPS26 protein levels in mouse primary cortical neurons and reduced APP processing, lowering endogenous Aβ42 and Aβ40 levels at low micromolar concentrations (5 µM) [26].”

    From Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer’s disease mouse model (2025) · cites this paper as [26]

    The Results section, “Pharmacological chaperones increase retromer in neurons,” reports that R55 increased both Vps35 and Vps26 protein levels, while R33 increased Vps35; it does not report an increase in Vps26 with R33. The Online Methods section, “Neuronal cultures,” identifies cortical neurons as the cultures used for western blot assays. Page numbers are unavailable in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • It has been shown that it is possible to pharmaceutically target the endosomal-sorting pathway with small molecules.

    “It remains to be seen whether this insight may lead to new tools for pharmaceutical intervention, but it has been shown that it is possible to pharmaceutically target the endosomal-sorting pathway with small molecules.41”

    From A common variant in CCDC93 protects against myocardial infarction and cardiovascular mortality by regulating endosomal trafficking of low-density lipoprotein receptor (2020) · cites this paper as [41]

  • Pharmacological stabilization of the retromer complex can attenuate amyloidogenic APP processing in primary cultured mouse neurons.

    “VPS26 haploinsufficiency in mice have been shown to elevate amyloidogenic APP processing, Aβ accumulation, and induce synaptic defects (Muhammad, Flores et al. 2008), and pharmacological stabilization of the retromer complex can attenuate amyloidogenic APP processing in primary cultured mouse neurons (Mecozzi, Berman et al. 2014).”

    From SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain (2026) · cites this paper as Mecozzi, Berman et al. 2014

  • Studies have provided proof-of-concept that retromer can be pharmacologically targeted.

    “Notably, studies have already provided the proof-of-concept that retromer can be pharmacologically targeted (Young et al., 2018; Mecozzi et al., 2014)”

    From The neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer's disease (2022) · cites this paper as Mecozzi et al., 2014

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Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 33

  1. Seaman, M.N. The retromer complex—endosomal protein recycling and beyond. J. Cell Sci. 125, 4693–4702 (2012). · DOI · Paper page
  2. Cullen, P.J. & Korswagen, H.C. Sorting nexins provide diversity for retromer-dependent trafficking events. Nat. Cell Biol. 14, 29–37 (2012). · DOI · Paper page
  3. Seaman, M.N. Recycle your receptors with retromer. Trends Cell Biol. 15, 68–75 (2005). · DOI · Paper page
  4. Small, S.A. et al. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann. Neurol. 58, 909–919 (2005). · DOI · Paper page
  5. Luo, Y. et al. Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation. Nat. Neurosci. 4, 231–232 (2001). · DOI · Paper page
  6. Jiang, Y. et al. Alzheimer's-related endosome dysfunction in Down syndrome is Aβ-independent but requires APP and is reversed by BACE-1 inhibition. Proc. Natl. Acad. Sci. USA 107, 1630–1635 (2010). · DOI
  7. Nikolaev, A., McLaughlin, T., O'Leary, D.D. & Tessier-Lavigne, M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457, 981–989 (2009). · DOI · Paper page
  8. Nishitomi, K. et al. BACE1 inhibition reduces endogenous Aβ and alters APP processing in wild-type mice. J. Neurochem. 99, 1555–1563 (2006). · DOI
  9. Small, S.A. & Gandy, S. Sorting through the cell biology of Alzheimer's disease: intracellular pathways to pathogenesis. Neuron 52, 15–31 (2006). · DOI
  10. Bhalla, A. et al. The location and trafficking routes of the neuronal retromer and its role in amyloid precursor protein transport. Neurobiol. Dis. 47, 126–134 (2012). · DOI · Paper page
  11. Vieira, S.I. et al. Retrieval of the Alzheimer's amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated. Mol. Neurodegener. 5, 40 (2010). · DOI
  12. Lane, R.F. et al. Diabetes-associated SorCS1 regulates Alzheimer's amyloid-β metabolism: evidence for involvement of SorL1 and the retromer complex. J. Neurosci. 30, 13110–13115 (2010). · DOI · Paper page
  13. Dodson, S.E. et al. LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. J. Neuropathol. Exp. Neurol. 65, 866–872 (2006). · DOI · Paper page
  14. Andersen, O.M. et al. Neuronal sorting protein–related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc. Natl. Acad. Sci. USA 102, 13461–13466 (2005). · DOI · Paper page
  15. Fjorback, A.W. et al. Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing. J. Neurosci. 32, 1467–1480 (2012). · DOI · Paper page
  16. Rogaeva, E. et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat. Genet. 39, 168–177 (2007). · DOI · Paper page
  17. Vardarajan, B.N. et al. Identification of Alzheimer disease-associated variants in genes that regulate retromer function. Neurobiol. Aging 33, 2231.e15–2231.e30 (2012). · DOI · Paper page
  18. Arighi, C.N., Hartnell, L.M., Aguilar, R.C., Haft, C.R. & Bonifacino, J.S. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J. Cell Biol. 165, 123–133 (2004). · DOI · Paper page
  19. Seaman, M.N. Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J. Cell Biol. 165, 111–122 (2004). · DOI · Paper page
  20. Vergés, M. et al. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor. Nat. Cell Biol. 6, 763–769 (2004). · DOI
  21. Norwood, S.J. et al. Assembly and solution structure of the core retromer protein complex. Traffic 12, 56–71 (2011). · DOI · Paper page
  22. MacLeod, D.A. et al. RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron 77, 425–439 (2013); erratum 77, 994 (2013). · DOI · Paper page
  23. Ringe, D. & Petsko, G.A. What are pharmacological chaperones and why are they interesting? J. Biol. 8, 80 (2009). · DOI
  24. Lieberman, R.L. et al. Structure of acid β-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat. Chem. Biol. 3, 101–107 (2007). · DOI
  25. Hierro, A. et al. Functional architecture of the retromer cargo-recognition complex. Nature 449, 1063–1067 (2007). · DOI · Paper page
  26. Mattos, C. & Ringe, D. Locating and characterizing binding sites on proteins. Nat. Biotechnol. 14, 595–599 (1996). · DOI
  27. Collins, B.M., Skinner, C.F., Watson, P.J., Seaman, M.N. & Owen, D.J. Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly. Nat. Struct. Mol. Biol. 12, 594–602 (2005). · DOI
  28. Swarbrick, J.D. et al. VPS29 is not an active metallo-phosphatase but is a rigid scaffold required for retromer interaction with accessory proteins. PLoS ONE 6, e20420 (2011). · DOI · Paper page
  29. Laurie, A.T. & Jackson, R.M. Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites. Bioinformatics 21, 1908–1916 (2005). · DOI
  30. Collins, B.M. et al. Structure of Vps26B and mapping of its interaction with the retromer protein complex. Traffic 9, 366–379 (2008). · DOI
  31. Shi, H., Rojas, R., Bonifacino, J.S. & Hurley, J.H. The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain. Nat. Struct. Mol. Biol. 13, 540–548 (2006). · DOI
  32. Landon, M.R., Lancia, D.R. Jr., Yu, J., Thiel, S.C. & Vajda, S. Identification of hot spots within druggable binding regions by computational solvent mapping of proteins. J. Med. Chem. 50, 1231–1240 (2007). · DOI
  33. Mucke, L. et al. High-level neuronal expression of Aβ 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058 (2000). · DOI · Paper page

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Metadata

Authors
Mecozzi, V. J., Berman, D. E., Simoes, S., Vetanovetz, C., Awal, M. R., Patel, V. M., Schneider, R. T., Petsko, G. A., Ringe, D., & Small, S. A.
ORCID
Berman, Diego E
Venue
Nature Chemical Biology
Publisher
Springer Science and Business Media LLC
Published
2014-04-20
Volume
10
Issue
6
Pages
443-449
ISSN
  • 1552-4450
  • 1552-4469
DOI
10.1038/nchembio.1508
PMC
PMC4076047
Cited by
216
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

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