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    Lennart Mucke, MD

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentNeurology
    Address1650 Owens St.
    San Francisco CA 94158
    Phone415-734-2504

       Overview 
       Overview
      Areas of investigation
      We study processes that result in memory loss and other major neurological deficits, with an emphasis on Alzheimerís disease (AD) and related neurodegenerative disorders. Our long-term goal is to advance the understanding of the healthy and the diseased central nervous system to a point where rational strategies can be developed for the prevention and cure of these conditions.

      Significance
      Molecules similar to those involved in neurodegenerative diseases are highly expressed in the nervous system of diverse species and appear to function in learning, synaptic plasticity, and regeneration. We are particularly curious about the roles of amyloid precursor proteins and apolipoprotein E in AD, and a-synuclein in Parkinsonís disease (PD). AD and PD are the most frequent neurodegenerative disorders. They erode peopleís ability to think and control their movements, two of the most critical and intriguing functions of the central nervous system. Both conditions are on the rise and neither can be prevented or cured. These facts underline the significance and urgency of our research efforts.

      Approaches
      We use transgenic mouse models and neural cultures to study potential pathogenic factors and pathways at the molecular, cellular, network, and behavioral level. Mouse models are also used to develop and evaluate novel treatment strategies. Their relevance is assessed through comparative studies of humans and postmortem tissues in collaboration with clinical programs.


      Contributions
      In AD-related transgenic models, we discovered that amyloid-ß peptides (Aß) can damage synapses and disrupt neural memory circuits independent of their deposition into the visible amyloid plaques that form in AD brains. The plaque-independent toxicity of Aß was inhibited by apolipoprotein E3, but not E4, which may relate to the differential effects of these molecules on AD risk and age of onset. Pathogenic interactions between Aß and a-synuclein worsened cognitive and motor deficits in doubly transgenic mice, a finding of potential relevance to the frequent overlap between AD and PD. Most recently, we discovered that neural network activity in AD-related mouse models fluctuates between abnormal excitation (epilepsy-like) and abnormal inhibition. Remarkably, reducing the protein tau effectively prevented these alterations as well as Aß-induced cognitive deficits. Ongoing studies aim to determine whether such network dysfunction also contributes to cognitive deficits in AD.

      Some questions addressed in ongoing studies

      How does Aß affect synaptic function and neuronal survival?
      How does tau reduction make the brain resistant against Aß-induced deficits?
      Can the beneficial effect of tau reduction be exploited therapeutically?
      Which drugs can block the aberrant network activity that Aß triggers?
      Will these drugs also normalize cognitive functions and prevent neurological decline in AD?
      What can the selective vulnerability of specific neuronal populations to different neurodegenerative disorders teach us about the uniqueness of the affected cells and the pathogenic cascades involved?


       ORNG Applications 
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       Bibliographic 
       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Minami SS, Min SW, Krabbe G, Wang C, Zhou Y, Asgarov R, Li Y, Martens LH, Elia LP, Ward ME, Mucke L, Farese RV, Gan L. Progranulin protects against amyloid ß deposition and toxicity in Alzheimer's disease mouse models. Nat Med. 2014 Oct; 20(10):1157-64.
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      2. Gheyara AL, Ponnusamy R, Djukic B, Craft RJ, Ho K, Guo W, Finucane MM, Sanchez PE, Mucke L. Tau reduction prevents disease in a mouse model of Dravet syndrome. Ann Neurol. 2014 Sep; 76(3):443-56.
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      3. Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-O M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L. Life extension factor klotho enhances cognition. Cell Rep. 2014 May 22; 7(4):1065-76.
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      4. Vossel KA, Beagle AJ, Rabinovici GD, Shu H, Lee SE, Naasan G, Hegde M, Cornes SB, Henry ML, Nelson AB, Seeley WW, Geschwind MD, Gorno-Tempini ML, Shih T, Kirsch HE, Garcia PA, Miller BL, Mucke L. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 2013 Sep 1; 70(9):1158-66.
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      5. Suberbielle E, Sanchez PE, Kravitz AV, Wang X, Ho K, Eilertson K, Devidze N, Kreitzer AC, Mucke L. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-ß. Nat Neurosci. 2013 May; 16(5):613-21.
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      6. Morris M, Hamto P, Adame A, Devidze N, Masliah E, Mucke L. Age-appropriate cognition and subtle dopamine-independent motor deficits in aged tau knockout mice. Neurobiol Aging. 2013 Jun; 34(6):1523-9.
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      7. Harris JA, Koyama A, Maeda S, Ho K, Devidze N, Dubal DB, Yu GQ, Masliah E, Mucke L. Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits. PLoS One. 2012; 7(9):e45881.
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      8. Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc Natl Acad Sci U S A. 2012 Oct 16; 109(42):E2895-903.
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      9. Mucke L, Selkoe DJ. Neurotoxicity of amyloid ß-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med. 2012 Jul; 2(7):a006338.
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      10. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012 Apr 27; 149(3):708-21.
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      11. Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012 Mar 16; 148(6):1204-22.
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      12. Minami SS, Sun B, Popat K, Kauppinen T, Pleiss M, Zhou Y, Ward ME, Floreancig P, Mucke L, Desai T, Gan L. Selective targeting of microglia by quantum dots. J Neuroinflammation. 2012; 9:22.
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      13. Morris M, Koyama A, Masliah E, Mucke L. Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease. PLoS One. 2011; 6(12):e29257.
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      14. Cissé M, Sanchez PE, Kim DH, Ho K, Yu GQ, Mucke L. Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice. J Neurosci. 2011 Jul 20; 31(29):10427-31.
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      15. Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron. 2011 May 12; 70(3):410-26.
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      16. Roberson ED, Halabisky B, Yoo JW, Yao J, Chin J, Yan F, Wu T, Hamto P, Devidze N, Yu GQ, Palop JJ, Noebels JL, Mucke L. Amyloid-ß/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J Neurosci. 2011 Jan 12; 31(2):700-11.
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      17. Palop JJ, Mucke L, Roberson ED. Quantifying biomarkers of cognitive dysfunction and neuronal network hyperexcitability in mouse models of Alzheimer's disease: depletion of calcium-dependent proteins and inhibitory hippocampal remodeling. Methods Mol Biol. 2011; 670:245-62.
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      18. Cissé M, Halabisky B, Harris J, Devidze N, Dubal DB, Sun B, Orr A, Lotz G, Kim DH, Hamto P, Ho K, Yu GQ, Mucke L. Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature. 2011 Jan 6; 469(7328):47-52.
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      19. Harris JA, Devidze N, Verret L, Ho K, Halabisky B, Thwin MT, Kim D, Hamto P, Lo I, Yu GQ, Palop JJ, Masliah E, Mucke L. Transsynaptic progression of amyloid-ß-induced neuronal dysfunction within the entorhinal-hippocampal network. Neuron. 2010 Nov 4; 68(3):428-41.
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      20. Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L. Tau reduction prevents Abeta-induced defects in axonal transport. Science. 2010 Oct 8; 330(6001):198.
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      21. Palop JJ, Mucke L. Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat Neurosci. 2010 Jul; 13(7):812-8.
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      22. Buttini M, Masliah E, Yu GQ, Palop JJ, Chang S, Bernardo A, Lin C, Wyss-Coray T, Huang Y, Mucke L. Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice. Am J Pathol. 2010 Aug; 177(2):563-9.
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      23. Sanchez-Mejia RO, Mucke L. Phospholipase A2 and arachidonic acid in Alzheimer's disease. Biochim Biophys Acta. 2010 Aug; 1801(8):784-90.
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      24. Harris JA, Devidze N, Halabisky B, Lo I, Thwin MT, Yu GQ, Bredesen DE, Masliah E, Mucke L. Many neuronal and behavioral impairments in transgenic mouse models of Alzheimer's disease are independent of caspase cleavage of the amyloid precursor protein. J Neurosci. 2010 Jan 6; 30(1):372-81.
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      25. Sun B, Halabisky B, Zhou Y, Palop JJ, Yu G, Mucke L, Gan L. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell. 2009 Dec 4; 5(6):624-33.
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      26. Palop JJ, Mucke L. Synaptic depression and aberrant excitatory network activity in Alzheimer's disease: two faces of the same coin? Neuromolecular Med. 2010 Mar; 12(1):48-55.
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      27. Mucke L. Neuroscience: Alzheimer's disease. Nature. 2009 Oct 15; 461(7266):895-7.
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      28. Khachaturian ZS, Snyder PJ, Doody R, Aisen P, Comer M, Dwyer J, Frank RA, Holzapfel A, Khachaturian AS, Korczyn AD, Roses A, Simpkins JW, Schneider LS, Albert MS, Egge R, Deves A, Ferris S, Greenberg BD, Johnson C, Kukull WA, Poirier J, Schenk D, Thies W, Gauthier S, Gilman S, Bernick C, Cummings JL, Fillit H, Grundman M, Kaye J, Mucke L, Reisberg B, Sano M, Pickeral O, Petersen RC, Mohs RC, Carrillo M, Corey-Bloom JP, Foster NL, Jacobsen S, Lee V, Potter WZ, Sabbagh MN, Salmon D, Trojanowski JQ, Wexler N, Bain LJ. A roadmap for the prevention of dementia II: Leon Thal Symposium 2008. Alzheimers Dement. 2009 Mar; 5(2):85-92.
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      29. Cisse M, Mucke L. Alzheimer's disease: A prion protein connection. Nature. 2009 Feb 26; 457(7233):1090-1.
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      30. Meilandt WJ, Cisse M, Ho K, Wu T, Esposito LA, Scearce-Levie K, Cheng IH, Yu GQ, Mucke L. Neprilysin overexpression inhibits plaque formation but fails to reduce pathogenic Abeta oligomers and associated cognitive deficits in human amyloid precursor protein transgenic mice. J Neurosci. 2009 Feb 18; 29(7):1977-86.
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      31. Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009 Apr; 66(4):435-40.
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      32. Cheng JS, Dubal DB, Kim DH, Legleiter J, Cheng IH, Yu GQ, Tesseur I, Wyss-Coray T, Bonaldo P, Mucke L. Collagen VI protects neurons against Abeta toxicity. Nat Neurosci. 2009 Feb; 12(2):119-21.
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      33. Sanchez-Mejia RO, Newman JW, Toh S, Yu GQ, Zhou Y, Halabisky B, Cissé M, Scearce-Levie K, Cheng IH, Gan L, Palop JJ, Bonventre JV, Mucke L. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nat Neurosci. 2008 Nov; 11(11):1311-8.
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      34. Tamgüney G, Giles K, Glidden DV, Lessard P, Wille H, Tremblay P, Groth DF, Yehiely F, Korth C, Moore RC, Tatzelt J, Rubinstein E, Boucheix C, Yang X, Stanley P, Lisanti MP, Dwek RA, Rudd PM, Moskovitz J, Epstein CJ, Cruz TD, Kuziel WA, Maeda N, Sap J, Ashe KH, Carlson GA, Tesseur I, Wyss-Coray T, Mucke L, Weisgraber KH, Mahley RW, Cohen FE, Prusiner SB. Genes contributing to prion pathogenesis. J Gen Virol. 2008 Jul; 89(Pt 7):1777-88.
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      35. Meilandt WJ, Yu GQ, Chin J, Roberson ED, Palop JJ, Wu T, Scearce-Levie K, Mucke L. Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci. 2008 May 7; 28(19):5007-17.
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      36. Gan L, Mucke L. Paths of convergence: sirtuins in aging and neurodegeneration. Neuron. 2008 Apr 10; 58(1):10-4.
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      37. Scearce-Levie K, Roberson ED, Gerstein H, Cholfin JA, Mandiyan VS, Shah NM, Rubenstein JL, Mucke L. Abnormal social behaviors in mice lacking Fgf17. Genes Brain Behav. 2008 Apr; 7(3):344-54.
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      38. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron. 2007 Sep 6; 55(5):697-711.
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      39. deIpolyi AR, Rankin KP, Mucke L, Miller BL, Gorno-Tempini ML. Spatial cognition and the human navigation network in AD and MCI. Neurology. 2007 Sep 4; 69(10):986-97.
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      40. Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, Puoliväli J, Lesné S, Ashe KH, Muchowski PJ, Mucke L. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem. 2007 Aug 17; 282(33):23818-28.
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      41. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007 May 4; 316(5825):750-4.
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      42. Chin J, Massaro CM, Palop JJ, Thwin MT, Yu GQ, Bien-Ly N, Bender A, Mucke L. Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease. J Neurosci. 2007 Mar 14; 27(11):2727-33.
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      43. Deipolyi AR, Fang S, Palop JJ, Yu GQ, Wang X, Mucke L. Altered navigational strategy use and visuospatial deficits in hAPP transgenic mice. Neurobiol Aging. 2008 Feb; 29(2):253-66.
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      44. Roberson ED, Mucke L. 100 years and counting: prospects for defeating Alzheimer's disease. Science. 2006 Nov 3; 314(5800):781-4.
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      45. Tesseur I, Zou K, Esposito L, Bard F, Berber E, Can JV, Lin AH, Crews L, Tremblay P, Mathews P, Mucke L, Masliah E, Wyss-Coray T. Deficiency in neuronal TGF-beta signaling promotes neurodegeneration and Alzheimer's pathology. J Clin Invest. 2006 Nov; 116(11):3060-9.
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      46. Palop JJ, Chin J, Mucke L. A network dysfunction perspective on neurodegenerative diseases. Nature. 2006 Oct 19; 443(7113):768-73.
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      47. Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L, Gan L. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron. 2006 Sep 21; 51(6):703-14.
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      48. Choi DS, Wang D, Yu GQ, Zhu G, Kharazia VN, Paredes JP, Chang WS, Deitchman JK, Mucke L, Messing RO. PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice. Proc Natl Acad Sci U S A. 2006 May 23; 103(21):8215-20.
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      49. Esposito L, Raber J, Kekonius L, Yan F, Yu GQ, Bien-Ly N, Puoliväli J, Scearce-Levie K, Masliah E, Mucke L. Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. J Neurosci. 2006 May 10; 26(19):5167-79.
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      50. Morris R, Mucke L. Alzheimer's disease: A needle from the haystack. Nature. 2006 Mar 16; 440(7082):284-5.
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      51. Palop JJ, Chin J, Bien-Ly N, Massaro C, Yeung BZ, Yu GQ, Mucke L. Vulnerability of dentate granule cells to disruption of arc expression in human amyloid precursor protein transgenic mice. J Neurosci. 2005 Oct 19; 25(42):9686-93.
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      52. Chin J, Palop JJ, Puoliväli J, Massaro C, Bien-Ly N, Gerstein H, Scearce-Levie K, Masliah E, Mucke L. Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci. 2005 Oct 19; 25(42):9694-703.
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      53. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L. SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem. 2005 Dec 2; 280(48):40364-74.
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      54. Rockenstein E, Mante M, Alford M, Adame A, Crews L, Hashimoto M, Esposito L, Mucke L, Masliah E. High beta-secretase activity elicits neurodegeneration in transgenic mice despite reductions in amyloid-beta levels: implications for the treatment of Alzheimer disease. J Biol Chem. 2005 Sep 23; 280(38):32957-67.
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      55. Esposito L, Gan L, Yu GQ, Essrich C, Mucke L. Intracellularly generated amyloid-beta peptide counteracts the antiapoptotic function of its precursor protein and primes proapoptotic pathways for activation by other insults in neuroblastoma cells. J Neurochem. 2004 Dec; 91(6):1260-74.
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      56. Cheng IH, Palop JJ, Esposito LA, Bien-Ly N, Yan F, Mucke L. Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nat Med. 2004 Nov; 10(11):1190-2.
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      57. Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, Liu S, Hegde A, Yan SF, Stern A, Luddy JS, Lue LF, Walker DG, Roher A, Buttini M, Mucke L, Li W, Schmidt AM, Kindy M, Hyslop PA, Stern DM, Du Yan SS. RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004 Oct 13; 23(20):4096-105.
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      58. Mucke L, Pitas RE. Food for thought: essential fatty acid protects against neuronal deficits in transgenic mouse model of AD. Neuron. 2004 Sep 2; 43(5):596-9.
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      59. Chin J, Palop JJ, Yu GQ, Kojima N, Masliah E, Mucke L. Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human amyloid precursor protein transgenic mice. J Neurosci. 2004 May 12; 24(19):4692-7.
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      60. Brecht WJ, Harris FM, Chang S, Tesseur I, Yu GQ, Xu Q, Dee Fish J, Wyss-Coray T, Buttini M, Mucke L, Mahley RW, Huang Y. Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J Neurosci. 2004 Mar 10; 24(10):2527-34.
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      61. Huang Y, Weisgraber KH, Mucke L, Mahley RW. Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease. J Mol Neurosci. 2004; 23(3):189-204.
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      62. Harris FM, Brecht WJ, Xu Q, Tesseur I, Kekonius L, Wyss-Coray T, Fish JD, Masliah E, Hopkins PC, Scearce-Levie K, Weisgraber KH, Mucke L, Mahley RW, Huang Y. Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc Natl Acad Sci U S A. 2003 Sep 16; 100(19):10966-71.
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      63. Palop JJ, Jones B, Kekonius L, Chin J, Yu GQ, Raber J, Masliah E, Mucke L. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc Natl Acad Sci U S A. 2003 Aug 5; 100(16):9572-7.
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      64. Buttini M, Yu GQ, Shockley K, Huang Y, Jones B, Masliah E, Mallory M, Yeo T, Longo FM, Mucke L. Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation. J Neurosci. 2002 Dec 15; 22(24):10539-48.
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      65. Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease--a double-edged sword. Neuron. 2002 Aug 1; 35(3):419-32.
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      66. Raber J, Bongers G, LeFevour A, Buttini M, Mucke L. Androgens protect against apolipoprotein E4-induced cognitive deficits. J Neurosci. 2002 Jun 15; 22(12):5204-9.
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      67. Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, Mucke L. beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc Natl Acad Sci U S A. 2001 Oct 9; 98(21):12245-50.
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      68. Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlogue L, Masliah E, Mucke L. TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat Med. 2001 May; 7(5):612-8.
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      69. Mucke L, Yu GQ, McConlogue L, Rockenstein EM, Abraham CR, Masliah E. Astroglial expression of human alpha(1)-antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice. Am J Pathol. 2000 Dec; 157(6):2003-10.
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      70. Wyss-Coray T, Mucke L. Ibuprofen, inflammation and Alzheimer disease. Nat Med. 2000 Sep; 6(9):973-4.
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      71. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000 Jun 1; 20(11):4050-8.
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      72. Wyss-Coray T, Lin C, von Euw D, Masliah E, Mucke L, Lacombe P. Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-beta 1 transgenic mice and functional metabolic correlates. Ann N Y Acad Sci. 2000 Apr; 903:317-23.
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      73. Raber J, Wong D, Yu GQ, Buttini M, Mahley RW, Pitas RE, Mucke L. Apolipoprotein E and cognitive performance. Nature. 2000 Mar 23; 404(6776):352-4.
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      74. Raber J, Akana SF, Bhatnagar S, Dallman MF, Wong D, Mucke L. Hypothalamic-pituitary-adrenal dysfunction in Apoe(-/-) mice: possible role in behavioral and metabolic alterations. J Neurosci. 2000 Mar 1; 20(5):2064-71.
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      75. Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science. 2000 Feb 18; 287(5456):1265-9.
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      76. Wyss-Coray T, Lin C, Sanan DA, Mucke L, Masliah E. Chronic overproduction of transforming growth factor-beta1 by astrocytes promotes Alzheimer's disease-like microvascular degeneration in transgenic mice. Am J Pathol. 2000 Jan; 156(1):139-50.
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      77. Buttini M, Akeefe H, Lin C, Mahley RW, Pitas RE, Wyss-Coray T, Mucke L. Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. Neuroscience. 2000; 97(2):207-10.
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      78. D'hooge R, Franck F, Mucke L, De Deyn PP. Age-related behavioural deficits in transgenic mice expressing the HIV-1 coat protein gp120. Eur J Neurosci. 1999 Dec; 11(12):4398-402.
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      79. Huang F, Buttini M, Wyss-Coray T, McConlogue L, Kodama T, Pitas RE, Mucke L. Elimination of the class A scavenger receptor does not affect amyloid plaque formation or neurodegeneration in transgenic mice expressing human amyloid protein precursors. Am J Pathol. 1999 Nov; 155(5):1741-7.
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      80. Xu X, Yang D, Wyss-Coray T, Yan J, Gan L, Sun Y, Mucke L. Wild-type but not Alzheimer-mutant amyloid precursor protein confers resistance against p53-mediated apoptosis. Proc Natl Acad Sci U S A. 1999 Jun 22; 96(13):7547-52.
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      81. Buttini M, Orth M, Bellosta S, Akeefe H, Pitas RE, Wyss-Coray T, Mucke L, Mahley RW. Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration. J Neurosci. 1999 Jun 15; 19(12):4867-80.
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      82. Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 1999 Jun; 23(2):297-308.
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      83. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci U S A. 1999 Mar 16; 96(6):3228-33.
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      84. Raber J, Wong D, Buttini M, Orth M, Bellosta S, Pitas RE, Mahley RW, Mucke L. Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females. Proc Natl Acad Sci U S A. 1998 Sep 1; 95(18):10914-9.
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      85. Masliah E, Raber J, Alford M, Mallory M, Mattson MP, Yang D, Wong D, Mucke L. Amyloid protein precursor stimulates excitatory amino acid transport. Implications for roles in neuroprotection and pathogenesis. J Biol Chem. 1998 May 15; 273(20):12548-54.
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      86. Bush TG, Savidge TC, Freeman TC, Cox HJ, Campbell EA, Mucke L, Johnson MH, Sofroniew MV. Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell. 1998 Apr 17; 93(2):189-201.
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      87. Krucker T, Toggas SM, Mucke L, Siggins GR. Transgenic mice with cerebral expression of human immunodeficiency virus type-1 coat protein gp120 show divergent changes in short- and long-term potentiation in CA1 hippocampus. Neuroscience. 1998 Apr; 83(3):691-700.
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      88. Buttini M, Westland CE, Masliah E, Yafeh AM, Wyss-Coray T, Mucke L. Novel role of human CD4 molecule identified in neurodegeneration. Nat Med. 1998 Apr; 4(4):441-6.
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      89. Xu X, Raber J, Yang D, Su B, Mucke L. Dynamic regulation of c-Jun N-terminal kinase activity in mouse brain by environmental stimuli. Proc Natl Acad Sci U S A. 1997 Nov 11; 94(23):12655-60.
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      90. Raeber AJ, Race RE, Brandner S, Priola SA, Sailer A, Bessen RA, Mucke L, Manson J, Aguzzi A, Oldstone MB, Weissmann C, Chesebro B. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J. 1997 Oct 15; 16(20):6057-65.
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      91. Wyss-Coray T, Masliah E, Mallory M, McConlogue L, Johnson-Wood K, Lin C, Mucke L. Amyloidogenic role of cytokine TGF-beta1 in transgenic mice and in Alzheimer's disease. Nature. 1997 Oct 9; 389(6651):603-6.
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      92. Wyss-Coray T, Borrow P, Brooker MJ, Mucke L. Astroglial overproduction of TGF-beta 1 enhances inflammatory central nervous system disease in transgenic mice . J Neuroimmunol. 1997 Jul; 77(1):45-50.
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      93. Raber J, Chen S, Mucke L, Feng L. Corticotropin-releasing factor and adrenocorticotrophic hormone as potential central mediators of OB effects. J Biol Chem. 1997 Jun 13; 272(24):15057-60.
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      94. Masliah E, Westland CE, Rockenstein EM, Abraham CR, Mallory M, Veinberg I, Sheldon E, Mucke L. Amyloid precursor proteins protect neurons of transgenic mice against acute and chronic excitotoxic injuries in vivo. Neuroscience. 1997 May; 78(1):135-46.
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      95. Mattson MP, Barger SW, Furukawa K, Bruce AJ, Wyss-Coray T, Mark RJ, Mucke L. Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer's disease. Brain Res Brain Res Rev. 1997 Feb; 23(1-2):47-61.
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      96. Raber J, Toggas SM, Lee S, Bloom FE, Epstein CJ, Mucke L. Central nervous system expression of HIV-1 Gp120 activates the hypothalamic-pituitary-adrenal axis: evidence for involvement of NMDA receptors and nitric oxide synthase. Virology. 1996 Dec 15; 226(2):362-73.
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      97. Zhao J, Paganini L, Mucke L, Gordon M, Refolo L, Carman M, Sinha S, Oltersdorf T, Lieberburg I, McConlogue L. Beta-secretase processing of the beta-amyloid precursor protein in transgenic mice is efficient in neurons but inefficient in astrocytes. J Biol Chem. 1996 Dec 6; 271(49):31407-11.
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      98. D'Hooge R, Nagels G, Westland CE, Mucke L, De Deyn PP. Spatial learning deficit in mice expressing human 751-amino acid beta-amyloid precursor protein. Neuroreport. 1996 Nov 4; 7(15-17):2807-11.
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      99. Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D. Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease. J Neurosci. 1996 Sep 15; 16(18):5795-811.
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      100. Mohajeri MH, Bartsch U, van der Putten H, Sansig G, Mucke L, Schachner M. Neurite outgrowth on non-permissive substrates in vitro is enhanced by ectopic expression of the neural adhesion molecule L1 by mouse astrocytes. Eur J Neurosci. 1996 Jun; 8(6):1085-97.
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      101. Wyss-Coray T, Masliah E, Toggas SM, Rockenstein EM, Brooker MJ, Lee HS, Mucke L. Dysregulation of signal transduction pathways as a potential mechanism of nervous system alterations in HIV-1 gp120 transgenic mice and humans with HIV-1 encephalitis. J Clin Invest. 1996 Feb 1; 97(3):789-98.
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      102. Mucke L, Abraham CR, Masliah E. Neurotrophic and neuroprotective effects of hAPP in transgenic mice. Ann N Y Acad Sci. 1996 Jan 17; 777:82-8.
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      103. Toggas SM, Masliah E, Mucke L. Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine. Brain Res. 1996 Jan 15; 706(2):303-7.
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      104. Toggas SM, Mucke L. Transgenic models in the study of AIDS dementia complex. Curr Top Microbiol Immunol. 1996; 206:223-41.
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      105. Masliah E, Ge N, Mucke L. Pathogenesis of HIV-1 associated neurodegeneration. Crit Rev Neurobiol. 1996; 10(1):57-67.
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      106. Rockenstein EM, McConlogue L, Tan H, Power M, Masliah E, Mucke L. Levels and alternative splicing of amyloid beta protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. J Biol Chem. 1995 Nov 24; 270(47):28257-67.
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      107. Race RE, Priola SA, Bessen RA, Ernst D, Dockter J, Rall GF, Mucke L, Chesebro B, Oldstone MB. Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent. Neuron. 1995 Nov; 15(5):1183-91.
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      108. Rall GF, Mucke L, Oldstone MB. Consequences of cytotoxic T lymphocyte interaction with major histocompatibility complex class I-expressing neurons in vivo. J Exp Med. 1995 Nov 1; 182(5):1201-12.
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      109. Borrow P, Cornell JL, Ruppe MD, Mucke L. Immunization-induced inflammatory infiltration of the central nervous system in transgenic mice expressing a microbial antigen in astrocytes. J Neuroimmunol. 1995 Sep; 61(2):133-49.
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      110. Wyss-Coray T, Feng L, Masliah E, Ruppe MD, Lee HS, Toggas SM, Rockenstein EM, Mucke L. Increased central nervous system production of extracellular matrix components and development of hydrocephalus in transgenic mice overexpressing transforming growth factor-beta 1. Am J Pathol. 1995 Jul; 147(1):53-67.
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      111. Verderber L, Johnson W, Mucke L, Sarthy V. Differential regulation of a glial fibrillary acidic protein-LacZ transgene in retinal astrocytes and Müller cells. Invest Ophthalmol Vis Sci. 1995 May; 36(6):1137-43.
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      112. Mucke L, Abraham CR, Ruppe MD, Rockenstein EM, Toggas SM, Mallory M, Alford M, Masliah E. Protection against HIV-1 gp120-induced brain damage by neuronal expression of human amyloid precursor protein. J Exp Med. 1995 Apr 1; 181(4):1551-6.
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      113. Lipton SA, Brenneman DE, Silverstein FS, Masliah E, Mucke L. gp120 and neurotoxicity in vivo. Trends Pharmacol Sci. 1995 Apr; 16(4):122.
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      114. Johnson WB, Ruppe MD, Rockenstein EM, Price J, Sarthy VP, Verderber LC, Mucke L. Indicator expression directed by regulatory sequences of the glial fibrillary acidic protein (GFAP) gene: in vivo comparison of distinct GFAP-lacZ transgenes. Glia. 1995 Mar; 13(3):174-84.
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      115. Mucke L, Masliah E, Campbell IL. Transgenic models to assess the neuropathogenic potential of HIV-1 proteins and cytokines. Curr Top Microbiol Immunol. 1995; 202:187-205.
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      116. Mucke L, Masliah E, Johnson WB, Ruppe MD, Alford M, Rockenstein EM, Forss-Petter S, Pietropaolo M, Mallory M, Abraham CR. Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice. Brain Res. 1994 Dec 15; 666(2):151-67.
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      117. Rall GF, Mucke L, Nerenberg M, Oldstone MB. A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes. J Neuroimmunol. 1994 Jun; 52(1):61-8.
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      118. Toggas SM, Masliah E, Rockenstein EM, Rall GF, Abraham CR, Mucke L. Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature. 1994 Jan 13; 367(6459):188-93.
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      119. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A. 1993 Nov 1; 90(21):10061-5.
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      120. Mucke L, Eddleston M. Astrocytes in infectious and immune-mediated diseases of the central nervous system. FASEB J. 1993 Oct; 7(13):1226-32.
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      121. Abraham CR, Kanemaru K, Mucke L. Expression of cathepsin G-like and alpha 1-antichymotrypsin-like proteins in reactive astrocytes. Brain Res. 1993 Sep 10; 621(2):222-32.
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      122. Eddleston M, Mucke L. Molecular profile of reactive astrocytes--implications for their role in neurologic disease. Neuroscience. 1993 May; 54(1):15-36.
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      123. Abraham CR, Razzaboni BL, Papastoitsis G, Picard E, Kanemaru K, Meckelein B, Mucke L. Purification and cloning of brain proteases capable of degrading the beta-amyloid precursor protein. Ann N Y Acad Sci. 1992 Dec 31; 674:174-9.
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      124. Mucke L, Oldstone MB. The expression of major histocompatibility complex (MHC) class I antigens in the brain differs markedly in acute and persistent infections with lymphocytic choriomeningitis virus (LCMV). J Neuroimmunol. 1992 Feb; 36(2-3):193-8.
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      125. Joly E, Mucke L, Oldstone MB. Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science. 1991 Sep 13; 253(5025):1283-5.
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      126. Mucke L, Oldstone MB, Morris JC, Nerenberg MI. Rapid activation of astrocyte-specific expression of GFAP-lacZ transgene by focal injury. New Biol. 1991 May; 3(5):465-74.
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      127. Ross ME, Evinger MJ, Hyman SE, Carroll JM, Mucke L, Comb M, Reis DJ, Joh TH, Goodman HM. Identification of a functional glucocorticoid response element in the phenylethanolamine N-methyltransferase promoter using fusion genes introduced into chromaffin cells in primary culture. J Neurosci. 1990 Feb; 10(2):520-30.
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      128. Berger JR, Mucke L. Prolonged survival and partial recovery in AIDS-associated progressive multifocal leukoencephalopathy. Neurology. 1988 Jul; 38(7):1060-5.
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      129. Benedek G, Mucke L, Norita M, Albowitz B, Creutzfeldt OD. Anterior ectosylvian visual area (AEV) of the cat: physiological properties. Prog Brain Res. 1988; 75:245-55.
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      130. Schalling M, Dagerlind A, Brene S, Petterson R, Kvist S, Brownstein M, Hyman SE, Mucke L, Goodman HM, Joh TH, et al. Localization of mRNA for phenylethanolamine N-methyltransferase (PNMT) using in situ hybridization. Acta Physiol Scand. 1987 Dec; 131(4):631-2.
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      131. Mucke L, Maciewicz R. Clinical management of neuropathic pain. Neurol Clin. 1987 Nov; 5(4):649-63.
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      132. Norita M, Mucke L, Benedek G, Albowitz B, Katoh Y, Creutzfeldt OD. Connections of the anterior ectosylvian visual area (AEV). Exp Brain Res. 1986; 62(2):225-40.
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      133. Mucke L, Norita M, Benedek G, Creutzfeldt O. Physiologic and anatomic investigation of a visual cortical area situated in the ventral bank of the anterior ectosylvian sulcus of the cat. Exp Brain Res. 1982; 46(1):1-11.
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