Publications

  1. Eschbach J, von Einem B, Muller K, Bayer H, Scheffold A, Morrison BE, Rudolph KL, Thal DR, Witting A, Weydt P, Otto M, Fauler M, Liss B, McLean PJ, La Spada AR, Ludolph AC, Weishaupt JH, Danzer KM. Mutual exacerbation of PGC-1alpha deregulation and alpha-synuclein oligomerization. Ann Neurol. 2014 Nov 01.
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  2. Wang L, Das U, Scott DA, Tang Y, McLean PJ, Roy S. alpha-Synuclein Multimers Cluster Synaptic Vesicles and Attenuate Recycling. Curr Biol. 2014 Oct 6; 24(19):2319-26. Epub 2014 Sep 25.
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  3. Winslow AR, Moussaud S, Zhu L, Post KL, Dickson DW, Berezovska O, McLean PJ. Convergence of pathology in dementia with Lewy bodies and Alzheimer's disease: a role for the novel interaction of alpha-synuclein and presenilin 1 in disease. Brain. 2014 Jul; 137(Pt 7):1958-70. Epub 2014 May 24.
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  4. Jones DR, Moussaud S, McLean P. Targeting heat shock proteins to modulate alpha-synuclein toxicity. Ther Adv Neurol Disord. 2014 Jan; 7(1):33-51.
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  5. McFarland NR, Dimant H, Kibuuka L, Ebrahimi-Fakhari D, Desjardins CA, Danzer KM, Danzer M, Fan Z, Schwarzschild MA, Hirst W, McLean PJ. Chronic treatment with novel small molecule Hsp90 inhibitors rescues striatal dopamine levels but not alpha-synuclein-induced neuronal cell loss. PLoS One. 2014; 9(1):e86048. Epub 2014 Jan 20.
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  6. Dimant H, Zhu L, Kibuuka LN, Fan Z, Hyman BT, McLean PJ. Direct Visualization of CHIP-Mediated Degradation of Alpha-Synuclein In Vivo: Implications for PD Therapeutics. PLoS One. 2014; 9(3):e92098. Epub 2014 Mar 24.
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  7. Moussaud S, Jones DR, Moussaud-Lamodiere EL, Delenclos M, Ross OA, McLean PJ. Alpha-synuclein and tau: teammates in neurodegeneration? Mol Neurodegener. 2014; 9:43. Epub 2014 Oct 29.
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  8. Neal KL, Shakerdge NB, Hou SS, Klunk WE, Mathis CA, Nesterov EE, Swager TM, McLean PJ, Bacskai BJ. Development and screening of contrast agents for in vivo imaging of Parkinson's disease. Mol Imaging Biol. 2013 Oct; 15(5):585-95.
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  9. Kalia LV, Kalia SK, McLean PJ, Lozano AM, Lang AE. alpha-Synuclein oligomers and clinical implications for Parkinson disease. Ann Neurol. 2013 Feb; 73(2):155-69. Epub 2012 Dec 7
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  10. Dimant H, Kalia S, Kalia L, Zhu L, Kibuuka L, Ebrahimi-Fakhari D, McFarland NR, Fan Z, Hyman BT, McLean PJ. Direct detection of alpha synuclein oligomers in vivo Acta Neuropathologica Commuinications. 2013; 1:6.
  11. Dimant H, Ebrahimi-Fakhari D, McLean PJ. Molecular chaperones and co-chaperones in Parkinson disease. Neuroscientist. 2012 Dec; 18(6):589-601. Epub 2012 Jul 24.
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  12. Ebrahimi-Fakhari D, Wahlster L, McLean PJ. Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathol. 2012 Aug; 124(2):153-72. Epub 2012 Jun 29.
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  13. Klucken J, Poehler AM, Ebrahimi-Fakhari D, Schneider J, Nuber S, Rockenstein E, Schlotzer-Schrehardt U, Hyman BT, McLean PJ, Masliah E, Winkler J. Alpha-synuclein aggregation involves a bafilomycin A 1-sensitive autophagy pathway. Autophagy. 2012 May 01; 8(5):754-66.
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  14. Donmez G, Arun A, Chung CY, McLean PJ, Lindquist S, Guarente L. SIRT1 protects against alpha-synuclein aggregation by activating molecular chaperones. J Neurosci. 2012 Jan 4; 32(1):124-32.
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  15. Ebrahimi‐Fakhari D, McLean PJ, Unni VK. Alpha‐synuclein’s degradation in vivo: opening a new (cranial) window on the roles of degradation pathways in Parkinson’s disease. Autophagy. 2012; 8(2):281-3 Epub 2012 Feb 1.
  16. Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, Vanderburg CR, McLean PJ. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener. 2012; 7:42. Epub 2012 Aug 24.
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  17. Danzer KM, McLean PJ. Drug targets from genetics: alpha-synuclein. CNS Neurol Disord Drug Targets. 2011 Sep 1; 10(6):712-23.
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  18. Hashimoto T, Adams KW, Fan Z, McLean PJ, Hyman BT. Characterization of oligomer formation of amyloid-beta peptide using a split-luciferase complementation assay. J Biol Chem. 2011 Aug 5; 286(31):27081-91. Epub 2011 Jun 07.
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  19. Unni VK, Ebrahimi-Fakhari D, Vanderburg CR, McLean PJ, Hyman BT. Studying protein degradation pathways in vivo using a cranial window-based approach. Methods. 2011 Mar; 53(3):194-200. Epub 2010 Dec 25.
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  20. Danzer KM, Ruf WP, Putcha P, Joyner D, Hashimoto T, Glabe C, Hyman BT, McLean PJ. Heat-shock protein 70 modulates toxic extracellular alpha-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J. 2011 Jan; 25(1):326-36. Epub 2010 Sep 27.
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  21. Mazzulli JR, Xu Y‐H, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. Gaucher disease glucocerebrosidase and alpha‐synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011; 146(1):37-52 Epub 2011 Jun 23.
  22. Ebrahimi‐Fakhari D, Cantuti‐Castelvetri I, Fan Z, Rockenstein E, Masliah E, Hyman BT, McLean PJ, Unni VK. Distinct Roles in vivo for the ubiquitin‐proteasome system and the autophagy‐lysosomal pathway in the degradation of alpha‐synuclein. J Neurosci. 2011; 31(41):14508-20.
  23. Ebrahimi‐Fakhari D, Wahlster L, McLean PJ. Molecular Chaperones in Parkinson’s Disease – Present and Future. J Parkinson’s Dis. 2011; 1(4):299-320.
  24. Kalia LV, Kalia SK, Chau H, Lozano AM, Hyman BT, McLean PJ. Ubiquitinylation of alpha-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5). PLoS One. 2011; 6(2):e14695. Epub 2011 Feb 16.
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  25. Kalia SK, Kalia LV, McLean PJ. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol Disord Drug Targets. 2010 Dec; 9(6):741-53.
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  26. Hillmer AS, Putcha P, Levin J, Hogen T, Hyman BT, Kretzschmar H, McLean PJ, Giese A. Converse modulation of toxic alpha-synuclein oligomers in living cells by N'-benzylidene-benzohydrazide derivates and ferric iron. Biochem Biophys Res Commun. 2010 Jan 1; 391(1):461-6. Epub 2009 Nov 13.
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  27. Unni VK, Weissman TA, Rockenstein E, Masliah E, McLean PJ, Hyman BT. In vivo imaging of alpha-synuclein in mouse cortex demonstrates stable expression and differential subcellular compartment mobility. PLoS One. 2010; 5(5):e10589. Epub 2010 May 11.
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  28. Putcha P, Danzer KM, Kranich LR, Scott A, Silinski M, Mabbett S, Hicks CD, Veal JM, Steed PM, Hyman BT, McLean PJ. Brain permeable small molecule inhibitors of Hsp90 prevent alpha‐synuclein oligomer formation and rescue alpha‐synuclein‐induced toxicity. J Pharm Exp Ther. 2010; 332(3):849-57 Epub 2009 Nov 24.
  29. McFarland NR, Lee JS, Hyman BT, McLean PJ. Comparison of Transduction Efficiency of Recombinant AAV Serotypes 1, 2, 5, and 8 in the Rat Nigrostriatal System. J Neurochem. 2009; 109(3):838-45 Epub 2009 Feb 24.
  30. McFarland NR, Fan Z, Xu K, Schwarzschild MA, Feany MB, Hyman BT, McLean PJ. Alpha‐synuclein S129 phosphorylation mutants do not alter nigrostriatal toxicity in a rat model of Parkinson disease. J Neuropathol Exp Neurol. 2009; 68(5):515-24.
  31. Outeiro TF, Klucken J, Bercury K, Tetzlaff JE, Putcha P, Oliveira LMA, Quintas A, McLean PJ, Hyman BT. Dopamine‐Induced Conformational Changes in Alpha‐Synuclein. PLoS ONE. 2009; 4(9):e6906.
  32. Chen L, Periquet M, Wang X, Negro A, McLean PJ, Hyman BT, Feany M. Serine Phosphorylation of alphasynuclein have opposing effects on neurotoxicity and soluble oligomer formation. J Clin Invest. 2009; 119(11):3257-65 Epub 2009 Oct 12.
  33. Yacoubian TA, Cantuti-Castelvetri I, Bouzou B, Asteris G, McLean PJ, Hyman BT, Standaert DG. Transcriptional dysregulation in a transgenic model of Parkinson disease. Neurobiol Dis. 2008 Mar; 29(3):515-28. Epub 2007 Nov 28.
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  34. Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ. Formation of toxic oligomeric alpha‐synuclein species in living cells. PLoS ONE. 2008; 3(4):e1867.
  35. Tetzlaff JE, Putcha P, Outeiro TF, Ivanov A, Berezovska O, Hyman BT, McLean PJ. Chip targets toxic alphasynuclein oligomers for degradation. J Biol Chem. 2008; 283(26):17962-8 Epub 2008 Apr 25.
  36. Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I, Ng J, Schulz‐Schaeffer W, Kretzschmar HA, McLean PJ, Trenkwalder C, Sarracino DA, Vonsattel JP, Locascio JJ, El‐Agnaf OM, Schlossmacher MG. Direct quantification of CSF alpha‐synuclein by ELISA and first cross‐sectional study in patients with neurodegeneration. Exp Neurol. 2008; 213(2):315-25 Epub 2008 Jun 14.
  37. Theodore S, Cao S, McLean PJ, Standaert DG. Targeted overexpression of human α‐synuclein triggers microglial activation and an adaptive immune respone in a mouse model of Parkinson’s disease. J Neuropathol Exp Neurol. 2008; 67(12):1149-58.
  38. St Martin JL, Klucken J, Outeiro TF, Nguyen P, Keller‐McGandy C, Cantuti‐Castelvetri I, Grammatopoulos TN, Standaert DG, Hyman BT, McLean PJ. Dopaminergic neuron loss and upregulation of chaperone protein mRNA induced by targeted overexpression of alpha‐synuclein in mouse substantia nigra. J Neurochem. 2007; 100(6):1449-57 Epub 2007 Jan 4.
  39. Outeiro TF, Kontopoulos E, Altman S, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet J‐C, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev A. Sirtuin 2 Inhibitors Rescue Alpha‐Synuclein‐Mediated Toxicity in Models of Parkinson’s Disease. Science. 2007; 317:516-9 Epub 2007 Jun 21.
  40. Klucken J, Ingelsson M, Shin Y, Irizarry MC, Hedley‐Whyte ET, Frosch M, Growdon J, McLean PJ, Hyman BT. Clinical and biochemical correlates of insoluble alpha‐synuclein in Dementia with Lewy Bodies. Acta Neuropathol. 2006; 111(2):101-8 Epub 2006 Feb 16.
  41. Giaime E, Sunyach C, Herrant M, Grosso S, Auberger P, McLean PJ, Checler F, Alves da Costa F. Caspase 3‐derived C‐terminal product of synphilin‐1 displays anti‐apoptotic function via modulation of the p53‐dependent cell death pathway. J Biol Chem. 2006; 28(17):11515-22 Epub 2006 Feb 22.
  42. Bodner R, Outeiro TF, Altman S, Maxwell MM, Cho SH, Hyman BT, McLean PJ, Young AB, Housman DE, Kazantsev AG. A novel approach to therapeutic interventions for Huntington’s and Parkinson’s diseases. Proc Natl Acad Sci. 2006; 103(11):4246-51 Epub 2006 Mar 6.
  43. Klucken J, Outeiro TF, Nguyen P, McLean PJ, Hyman BT. Detection of novel intracellular α‐synuclein oligomeric species by fluorescence lifetime imaging. FASEB J. 2006; 20(12):2050-7.
  44. Outeiro TF, Klucken J, Strathearn KE, Liu F, Nguyen P, Rochet J‐C, Hyman BT, McLean PJ. Small heat shock proteins protect against alpha‐synuclein‐induced toxicity and aggregation. Biochem Biophys Res Comm. 2006; 351(3):631-8 Epub 2006 Oct 26.
  45. Shin Y, Klucken J, Patterson C, Hyman BT, McLean PJ. The co‐chaperone carboxyl terminus of Hsp70‐interacting Protein (CHIP) mediates α‐synuclein degradation decisions between proteasomal and lysosomal pathways. J Biol Chem. 2005; 280(25):23727-34.
  46. Spires TL, Meyer‐Leuhmann M, Stern EA, McLean PJ, Skoch J, Nguyen PT, Bacskai BJ, Hyman BT. Dendritic spine abnormalities in APP transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neuroscience. 2005; 25:7278-87.
  47. Cantuti‐Castelvetri I, Klucken J, Ingelsson M, Ramasamy K, McLean PJ, Frosch MP, Hyman BT, Standaert DG. Alpha‐synuclein and chaperones in dementia with Lewy bodies. J Neuropathol Exp Neurol. 2005; 64(12):1058-66.
  48. Klucken J, Shin Y, Masliah E, Hyman BT, McLean PJ. Hsp70 reduces alpha‐synuclein aggregation and toxicity. J Biol Chem. 2004; 279:25497-502.
  49. McLean PJ, Klucken J, Shin Y, Hyman BT. Geldanamycin induces Hsp70 and prevents α‐synuclein aggregation and toxicity in vitro. Biochem Biophys Res Comm. 2004; 321(3):665-9.
  50. Klucken J, Shin Y, Hyman BT, McLean PJ. A single amino acid substitution differentiates Hsp70 dependent effects on α‐synuclein degradation and toxicity. Biochem Biophys Res Comm. 2004; 325(1):367-74.
  51. Klucken J, McLean PJ, Gomez‐Tortosa E, Ingelsson M, Hyman BT. Neuritic alterations and neural system dysfunction in Alzheimer’s disease and dementia with Lewy bodies. Neurochem Res. 2003; 11:1683-91.
  52. McLean PJ, Hyman BT. An alternatively spliced form of rodent α‐synuclein forms intracellular inclusions in vitro: role of the carboxy‐terminus in α‐synuclein aggregation. Neurosci Letts. 2002; 323(3):219-23.
  53. McLean PJ, Kawamata H, Shariff S, Hewett J, Sharma N, Ueda K, Breakefield XO, Hyman BT. TorsinA and heat shock proteins act as molecular chaperones: suppression of α‐synuclein aggregation in vitro. J Neurochem. 2002; 83:846-54.
  54. McLean PJ, Kawamata H, Hyman BT. α‐SynucleinEGFP fusion proteins form proteasome sensitive inclusions in primary neurons. Neuroscience. 2001; 104:901-12.
  55. Kawamata H, McLean PJ, Sharma N, Hyman BT. Interaction of α‐synuclein and synphilin‐1: Effect of Parkinson’s disease associated mutations. J Neurochem. 2001; 77(3):929-34.
  56. Sharma N, McLean PJ, Kawamata H, Hyman BT. Alpha‐synuclein has an altered conformation and shows a tight intermolecular interaction with ubiquitin in Lewy bodies. Acta Neuropathol. 2001; 104:329-34.
  57. Sharma N, Hewett J, Ozelius LJ, Ramesh V, McLean PJ, Breakefield XO, Hyman BT. A close association of torsinA and alpha‐synuclein in Lewy bodies: A fluorescence energy transfer study. Am J Pathol. 2001; 59:339-44.
  58. McLean PJ, Shpektor D, Bandyopandhyay S, Russek SJ, Farb DH. A minimal promoter for the GABAA receptor α6 subunit gene controls tissue specificity. J Neurochem. 2000; 74(5):1858-69.
  59. Berezovska O, Jack C, McLean P, Aster JC, Hicks C, Xia W, Wolfe MS, Kimberly WT, Weinmaster G, Selkoe DJ, Hyman BT. Aspartate mutations in presenilin and γ‐secretase inhibitors both impair Notch1 proteolysis and nuclear translocation with relative preservation of Notch signaling. J Neurochem. 2000; 75(2):583-93.
  60. McLean PJ, Kawamata H, Ribich S, Hyman BT. Membrane association and protein conformation of α‐synuclein in intact neurons: Effect of Parkinson disease linked mutations. J Biol Chem. 2000; 275(12):8812-6.
  61. Berezovska O, McLean P, Knowles R, Lu FM, Lux SE, Hyman BT. Notch transfection affects neurite outgrowth in post‐mitotic primary neurons. Neuroscience. 1999; 93(2):433-9.
  62. Berezovska O, Frosch M, McLean P, Knowles R, Koo E, Kang D, Lu FM, Lux SE, Shen J, Tonegawa S, Hyman BT. The Alzheimer‐related gene Presenilin 1 facilitates Notch 1 effect on neurite outgrowth in primary mammalian neurons. Molecular Brain Research. 1999; 69(2):273-80.
  63. McLean PJ, Farb DH, Russek SJ. Mapping of the α4 subunit gene (GABRA4) to human chromosome 4 defines an α2‐α4‐β1‐γ1 gene cluster: Further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster. Genomics. 1995; 26:580-6.