Proteolytic clearance of extracellular α-synuclein as a new therapeutic approach against Parkinson disease

References

• Frost B, Diamond MI. Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci 2010; 11:155 - 9; PMID: 20029438
   PubMed Web of Science ®Google Scholar
• Saiki S, Sato S, Hattori N. Molecular pathogenesis of Parkinson’s disease: update. J Neurol Neurosurg Psychiatry 2012; 83:430 - 6; http://dx.doi.org/10.1136/jnnp-2011-301205; PMID: 22138181
   PubMed Web of Science ®Google Scholar
• Surguchov A. Chapter 6 Molecular and Cellular Biology of Synucleins. 2008; 270:225-317.
   Google Scholar
• Martin I, Dawson VL, Dawson TM. Recent advances in the genetics of Parkinson’s disease. Annu Rev Genomics Hum Genet 2011; 12:301 - 25; http://dx.doi.org/10.1146/annurev-genom-082410-101440; PMID: 21639795
   PubMed Web of Science ®Google Scholar
• Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet 2009; 41:1303 - 7; http://dx.doi.org/10.1038/ng.485; PMID: 19915576
   PubMed Web of Science ®Google Scholar
• Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet 2009; 41:1308 - 12; http://dx.doi.org/10.1038/ng.487; PMID: 19915575
   PubMed Web of Science ®Google Scholar
• Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L. Pathological roles of α-synuclein in neurological disorders. Lancet Neurol 2011; 10:1015 - 25; http://dx.doi.org/10.1016/S1474-4422(11)70213-7; PMID: 22014436
   PubMed Web of Science ®Google Scholar
• El-Agnaf OM, Salem SA, Paleologou KE, Cooper LJ, Fullwood NJ, Gibson MJ, et al. Alpha-synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. FASEB J 2003; 17:1945 - 7; PMID: 14519670
   PubMed Web of Science ®Google Scholar
• Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Döring F, Trenkwalder C, Schlossmacher MG. α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 2011; 10:230 - 40; http://dx.doi.org/10.1016/S1474-4422(11)70014-X; PMID: 21317042
   PubMed Web of Science ®Google Scholar
• Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T, et al. Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 2010; 75:1766 - 72; http://dx.doi.org/10.1212/WNL.0b013e3181fd613b; PMID: 20962290
   PubMed Web of Science ®Google Scholar
• Lee HJ, Patel S, Lee SJ. Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 2005; 25:6016 - 24; http://dx.doi.org/10.1523/JNEUROSCI.0692-05.2005; PMID: 15976091
   PubMed Web of Science ®Google Scholar
• Jang A, Lee HJ, Suk JE, Jung JW, Kim KP, Lee SJ. Non-classical exocytosis of alpha-synuclein is sensitive to folding states and promoted under stress conditions. J Neurochem 2010; 113:1263 - 74; PMID: 20345754
   PubMed Web of Science ®Google Scholar
• Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 2010; 30:6838 - 51; http://dx.doi.org/10.1523/JNEUROSCI.5699-09.2010; PMID: 20484626
   PubMed Web of Science ®Google Scholar
• Alvarez-Erviti L, Couch Y, Richardson J, Cooper JM, Wood MJ. Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line. Neurosci Res 2011; 69:337 - 42; http://dx.doi.org/10.1016/j.neures.2010.12.020; PMID: 21255620
   PubMed Web of Science ®Google Scholar
• Sung JY, Kim J, Paik SR, Park JH, Ahn YS, Chung KC. Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. J Biol Chem 2001; 276:27441 - 8; http://dx.doi.org/10.1074/jbc.M101318200; PMID: 11316809
   PubMed Web of Science ®Google Scholar
• Ahn KJ, Paik SR, Chung KC, Kim J. Amino acid sequence motifs and mechanistic features of the membrane translocation of alpha-synuclein. J Neurochem 2006; 97:265 - 79; http://dx.doi.org/10.1111/j.1471-4159.2006.03731.x; PMID: 16524375
   PubMed Web of Science ®Google Scholar
• Lee HJ, Suk JE, Bae EJ, Lee JH, Paik SR, Lee SJ. Assembly-dependent endocytosis and clearance of extracellular alpha-synuclein. Int J Biochem Cell Biol 2008; 40:1835 - 49; http://dx.doi.org/10.1016/j.biocel.2008.01.017; PMID: 18291704
   PubMed Web of Science ®Google Scholar
• Park JY, Kim KS, Lee SB, Ryu JS, Chung KC, Choo YK, et al. On the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft. J Neurochem 2009; 110:400 - 11; http://dx.doi.org/10.1111/j.1471-4159.2009.06150.x; PMID: 19457104
   PubMed Web of Science ®Google Scholar
• El-Agnaf OM, Jakes R, Curran MD, Middleton D, Ingenito R, Bianchi E, et al. Aggregates from mutant and wild-type alpha-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of beta-sheet and amyloid-like filaments. FEBS Lett 1998; 440:71 - 5; http://dx.doi.org/10.1016/S0014-5793(98)01418-5; PMID: 9862428
   PubMed Web of Science ®Google Scholar
• Seo JH, Rah JC, Choi SH, Shin JK, Min K, Kim HS, et al. Alpha-synuclein regulates neuronal survival via Bcl-2 family expression and PI3/Akt kinase pathway. FASEB J 2002; 16:1826 - 8; PMID: 12223445
   PubMed Web of Science ®Google Scholar
• Klegeris A, Giasson BI, Zhang H, Maguire J, Pelech S, McGeer PL. Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. FASEB J 2006; 20:2000 - 8; http://dx.doi.org/10.1096/fj.06-6183com; PMID: 17012252
   PubMed Web of Science ®Google Scholar
• Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, Kim WK, et al. Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol 2010; 185:615 - 23; http://dx.doi.org/10.4049/jimmunol.0903480; PMID: 20511551
   PubMed Web of Science ®Google Scholar
• Lee SB, Park SM, Ahn KJ, Chung KC, Paik SR, Kim J. Identification of the amino acid sequence motif of alpha-synuclein responsible for macrophage activation. Biochem Biophys Res Commun 2009; 381:39 - 43; http://dx.doi.org/10.1016/j.bbrc.2009.02.002; PMID: 19351591
   PubMed Web of Science ®Google Scholar
• Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 2005; 19:533 - 42; http://dx.doi.org/10.1096/fj.04-2751com; PMID: 15791003
   PubMed Web of Science ®Google Scholar
• Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 2008; 14:504 - 6; http://dx.doi.org/10.1038/nm1747; PMID: 18391962
   PubMed Web of Science ®Google Scholar
• Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 2008; 14:501 - 3; http://dx.doi.org/10.1038/nm1746; PMID: 18391963
   PubMed Web of Science ®Google Scholar
• Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24:197 - 211; http://dx.doi.org/10.1016/S0197-4580(02)00065-9; PMID: 12498954
   PubMed Web of Science ®Google Scholar
• Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A 2009; 106:13010 - 5; http://dx.doi.org/10.1073/pnas.0903691106; PMID: 19651612
   PubMed Web of Science ®Google Scholar
• Luk KC, Song C, O’Brien P, Stieber A, Branch JR, Brunden KR, et al. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci U S A 2009; 106:20051 - 6; PMID: 19892735
   PubMed Web of Science ®Google Scholar
• Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, et al. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011; 72:57 - 71; http://dx.doi.org/10.1016/j.neuron.2011.08.033; PMID: 21982369
   PubMed Web of Science ®Google Scholar
• Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L, Paul G, et al. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest 2011; 121:715 - 25; http://dx.doi.org/10.1172/JCI43366; PMID: 21245577
   PubMed Web of Science ®Google Scholar
• Kordower JH, Dodiya HB, Kordower AM, Terpstra B, Paumier K, Madhavan L, et al. Transfer of host-derived α synuclein to grafted dopaminergic neurons in rat. Neurobiol Dis 2011; 43:552 - 7; http://dx.doi.org/10.1016/j.nbd.2011.05.001; PMID: 21600984
   PubMed Web of Science ®Google Scholar
• Mougenot AL, Nicot S, Bencsik A, Morignat E, Verchère J, Lakhdar L, et al. Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 2012; 33:2225 - 8; http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.022; PMID: 21813214
   PubMed Web of Science ®Google Scholar
• Buerger K, Ewers M, Pirttilä T, Zinkowski R, Alafuzoff I, Teipel SJ, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain 2006; 129:3035 - 41; http://dx.doi.org/10.1093/brain/awl269; PMID: 17012293
   PubMed Web of Science ®Google Scholar
• Vandermeeren M, Mercken M, Vanmechelen E, Six J, van de Voorde A, Martin JJ, et al. Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 1993; 61:1828 - 34; http://dx.doi.org/10.1111/j.1471-4159.1993.tb09823.x; PMID: 8228996
   PubMed Web of Science ®Google Scholar
• Chai X, Dage JL, Citron M. Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol Dis 2012; 48:356 - 66; http://dx.doi.org/10.1016/j.nbd.2012.05.021; PMID: 22668776
   PubMed Web of Science ®Google Scholar
• Saman S, Kim W, Raya M, Visnick Y, Miro S, Saman S, et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem 2012; 287:3842 - 9; http://dx.doi.org/10.1074/jbc.M111.277061; PMID: 22057275
   PubMed Web of Science ®Google Scholar
• Simón D, García-García E, Royo F, Falcón-Pérez JM, Avila J. Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Lett 2012; 586:47 - 54; http://dx.doi.org/10.1016/j.febslet.2011.11.022; PMID: 22138183
   PubMed Web of Science ®Google Scholar
• Frost B, Jacks RL, Diamond MI. Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 2009; 284:12845 - 52; http://dx.doi.org/10.1074/jbc.M808759200; PMID: 19282288
   PubMed Web of Science ®Google Scholar
• Gómez-Ramos A, Díaz-Hernández M, Cuadros R, Hernández F, Avila J. Extracellular tau is toxic to neuronal cells. FEBS Lett 2006; 580:4842 - 50; http://dx.doi.org/10.1016/j.febslet.2006.07.078; PMID: 16914144
   PubMed Web of Science ®Google Scholar
• Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 2009; 11:909 - 13; http://dx.doi.org/10.1038/ncb1901; PMID: 19503072
   PubMed Web of Science ®Google Scholar
• Guo JL, Lee VM. Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J Biol Chem 2011; 286:15317 - 31; http://dx.doi.org/10.1074/jbc.M110.209296; PMID: 21372138
   PubMed Web of Science ®Google Scholar
• Zetterström P,, Andersen PM, Brännström T, Marklund SL. Misfolded superoxide dismutase-1 in CSF from amyotrophic lateral sclerosis patients. J Neurochem 2011; 117:91 - 9; http://dx.doi.org/10.1111/j.1471-4159.2011.07177.x; PMID: 21226712
   PubMed Web of Science ®Google Scholar
• Mondola P, Annella T, Santillo M, Santangelo F. Evidence for secretion of cytosolic CuZn superoxide dismutase by Hep G2 cells and human fibroblasts. Int J Biochem Cell Biol 1996; 28:677 - 81; http://dx.doi.org/10.1016/1357-2725(96)00004-0; PMID: 8673732
   PubMed Web of Science ®Google Scholar
• Urushitani M, Sik A, Sakurai T, Nukina N, Takahashi R, Julien JP. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat Neurosci 2006; 9:108 - 18; http://dx.doi.org/10.1038/nn1603; PMID: 16369483
   PubMed Web of Science ®Google Scholar
• Zhao W, Beers DR, Henkel JS, Zhang W, Urushitani M, Julien JP, et al. Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia 2010; 58:231 - 43; http://dx.doi.org/10.1002/glia.20919; PMID: 19672969
   PubMed Web of Science ®Google Scholar
• Chia R, Tattum MH, Jones S, Collinge J, Fisher EM, Jackson GS. Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis. PLoS One 2010; 5:e10627; http://dx.doi.org/10.1371/journal.pone.0010627; PMID: 20498711
   PubMed Web of Science ®Google Scholar
• Münch C, O’Brien J, Bertolotti A. Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. Proc Natl Acad Sci U S A 2011; 108:3548 - 53; http://dx.doi.org/10.1073/pnas.1017275108; PMID: 21321227
   PubMed Web of Science ®Google Scholar
• Ren PH, Lauckner JE, Kachirskaia I, Heuser JE, Melki R, Kopito RR. Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates. Nat Cell Biol 2009; 11:219 - 25; http://dx.doi.org/10.1038/ncb1830; PMID: 19151706
   PubMed Web of Science ®Google Scholar
• Miller G. Neurodegeneration. Could they all be prion diseases?. Science 2009; 326:1337 - 9; http://dx.doi.org/10.1126/science.326.5958.1337; PMID: 19965731
   PubMed Web of Science ®Google Scholar
• Goedert M, Clavaguera F, Tolnay M. The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 2010; 33:317 - 25; http://dx.doi.org/10.1016/j.tins.2010.04.003; PMID: 20493564
   PubMed Web of Science ®Google Scholar
• Lee SJ, Desplats P, Sigurdson C, Tsigelny I, Masliah E. Cell-to-cell transmission of non-prion protein aggregates. Nat Rev Neurol 2010; 6:702 - 6; http://dx.doi.org/10.1038/nrneurol.2010.145; PMID: 21045796
   PubMed Web of Science ®Google Scholar
• Krammer C, Schätzl HM, Vorberg I. Prion-like propagation of cytosolic protein aggregates: insights from cell culture models. Prion 2009; 3:206 - 12; http://dx.doi.org/10.4161/pri.3.4.10013; PMID: 19901539
   PubMed Web of Science ®Google Scholar
• Aguzzi A, Rajendran L. The transcellular spread of cytosolic amyloids, prions and prionoids. Neuron 2009; 64:783 - 90; http://dx.doi.org/10.1016/j.neuron.2009.12.016; PMID: 20064386
   PubMed Web of Science ®Google Scholar
• Iwata A, Maruyama M, Akagi T, Hashikawa T, Kanazawa I, Tsuji S, et al. Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Hum Mol Genet 2003; 12:2625 - 35; http://dx.doi.org/10.1093/hmg/ddg283; PMID: 12928483
   PubMed Web of Science ®Google Scholar
• Sung JY, Park SM, Lee CH, Um JW, Lee HJ, Kim J, et al. Proteolytic cleavage of extracellular secreted alpha-synuclein via matrix metalloproteinases. J Biol Chem 2005; 280:25216 - 24; http://dx.doi.org/10.1074/jbc.M503341200; PMID: 15863497
   PubMed Web of Science ®Google Scholar
• Mishizen-Eberz AJ, Norris EH, Giasson BI, Hodara R, Ischiropoulos H, Lee VM, et al. Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein. Biochemistry 2005; 44:7818 - 29; http://dx.doi.org/10.1021/bi047846q; PMID: 15909996
   PubMed Web of Science ®Google Scholar
• Sevlever D, Jiang P, Yen SH. Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species. Biochemistry 2008; 47:9678 - 87; http://dx.doi.org/10.1021/bi800699v; PMID: 18702517
   PubMed Web of Science ®Google Scholar
• Kim KS, Choi YR, Park JY, Lee JH, Kim DK, Lee SJ, et al. Proteolytic cleavage of extracellular α-synuclein by plasmin: implications for Parkinson disease. J Biol Chem 2012; 287:24862 - 72; http://dx.doi.org/10.1074/jbc.M112.348128; PMID: 22619171
   PubMed Web of Science ®Google Scholar
• Ogawa K, Yamada T, Tsujioka Y, Taguchi J, Takahashi M, Tsuboi Y, et al. Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer’s disease and Parkinson’s disease. Psychiatry Clin Neurosci 2000; 54:419 - 26; http://dx.doi.org/10.1046/j.1440-1819.2000.00731.x; PMID: 10997858
   PubMed Web of Science ®Google Scholar
• Tatebe H, Watanabe Y, Kasai T, Mizuno T, Nakagawa M, Tanaka M, et al. Extracellular neurosin degrades α-synuclein in cultured cells. Neurosci Res 2010; 67:341 - 6; http://dx.doi.org/10.1016/j.neures.2010.04.008; PMID: 20403393
   PubMed Web of Science ®Google Scholar
• Spencer B, Michael S, Shen J, Kosberg K, Rockenstein E, Patrick C, et al. Lentivirus Mediated Delivery of Neurosin Promotes Clearance of Wild-type α-Synuclein and Reduces the Pathology in an α-Synuclein Model of LBD. Mol Ther 2012; http://dx.doi.org/10.1038/mt.2012.66; PMID: 22508489
   PubMed Web of Science ®Google Scholar
• Schaller J, Gerber SS. The plasmin-antiplasmin system: structural and functional aspects. Cell Mol Life Sci 2011; 68:785 - 801; http://dx.doi.org/10.1007/s00018-010-0566-5; PMID: 21136135
   PubMed Web of Science ®Google Scholar
• Dotti CG, Galvan C, Ledesma MD. Plasmin deficiency in Alzheimer’s disease brains: causal or casual?. Neurodegener Dis 2004; 1:205 - 12; http://dx.doi.org/10.1159/000080987; PMID: 16908991
   PubMed Web of Science ®Google Scholar
• Syrovets T, Simmet T. Novel aspects and new roles for the serine protease plasmin. Cell Mol Life Sci 2004; 61:873 - 85; http://dx.doi.org/10.1007/s00018-003-3348-5; PMID: 15095009
   PubMed Web of Science ®Google Scholar
• Sheehan JJ, Tsirka SE. Fibrin-modifying serine proteases thrombin, tPA and plasmin in ischemic stroke: a review. Glia 2005; 50:340 - 50; http://dx.doi.org/10.1002/glia.20150; PMID: 15846799
   PubMed Web of Science ®Google Scholar
• Van Nostrand WE, Porter M. Plasmin cleavage of the amyloid beta-protein: alteration of secondary structure and stimulation of tissue plasminogen activator activity. Biochemistry 1999; 38:11570 - 6; http://dx.doi.org/10.1021/bi990610f; PMID: 10471309
   PubMed Web of Science ®Google Scholar
• Tucker HM, Kihiko M, Caldwell JN, Wright S, Kawarabayashi T, Price D, et al. The plasmin system is induced by and degrades amyloid-beta aggregates. J Neurosci 2000; 20:3937 - 46; PMID: 10818128
   PubMed Web of Science ®Google Scholar
• Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, et al. Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med 2000; 6:143 - 50; http://dx.doi.org/10.1038/77399; PMID: 10655101
   PubMed Web of Science ®Google Scholar
• Ledesma MD, Da Silva JS, Crassaerts K, Delacourte A, De Strooper B, Dotti CG. Brain plasmin enhances APP alpha-cleavage and Abeta degradation and is reduced in Alzheimer’s disease brains. EMBO Rep 2000; 1:530 - 5; PMID: 11263499
   PubMed Web of Science ®Google Scholar
• Backstrom JR, Lim GP, Cullen MJ, Tökés ZA. Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-beta peptide (1-40). J Neurosci 1996; 16:7910 - 9; PMID: 8987819
   PubMed Web of Science ®Google Scholar
• Qiu WQ, Walsh DM, Ye Z, Vekrellis K, Zhang J, Podlisny MB, et al. Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J Biol Chem 1998; 273:32730 - 8; http://dx.doi.org/10.1074/jbc.273.49.32730; PMID: 9830016
   PubMed Web of Science ®Google Scholar
• Hemming ML, Patterson M, Reske-Nielsen C, Lin L, Isacson O, Selkoe DJ. Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degrading protease: a novel therapeutic approach to Alzheimer disease. PLoS Med 2007; 4:e262; http://dx.doi.org/10.1371/journal.pmed.0040262; PMID: 17760499
   PubMedGoogle Scholar
• Jacobsen JS, Comery TA, Martone RL, Elokdah H, Crandall DL, Oganesian A, et al. Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade. Proc Natl Acad Sci U S A 2008; 105:8754 - 9; http://dx.doi.org/10.1073/pnas.0710823105; PMID: 18559859
   PubMed Web of Science ®Google Scholar
• Leissring MA. The AbetaCs of Abeta-cleaving proteases. J Biol Chem 2008; 283:29645 - 9; http://dx.doi.org/10.1074/jbc.R800022200; PMID: 18723506
   PubMed Web of Science ®Google Scholar
• Miners JS, Barua N, Kehoe PG, Gill S, Love S. Aβ-degrading enzymes: potential for treatment of Alzheimer disease. J Neuropathol Exp Neurol 2011; 70:944 - 59; http://dx.doi.org/10.1097/NEN.0b013e3182345e46; PMID: 22002425
   PubMed Web of Science ®Google Scholar
• Nalivaeva NN, Beckett C, Belyaev ND, Turner AJ. Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer’s disease?. J Neurochem 2012; 120:Suppl 1 167 - 85; http://dx.doi.org/10.1111/j.1471-4159.2011.07510.x; PMID: 22122230
   PubMed Web of Science ®Google Scholar
• Luhr KM, Nordström EK, Löw P, Ljunggren HG, Taraboulos A, Kristensson K. Scrapie protein degradation by cysteine proteases in CD11c+ dendritic cells and GT1-1 neuronal cells. J Virol 2004; 78:4776 - 82; http://dx.doi.org/10.1128/JVI.78.9.4776-4782.2004; PMID: 15078959
   PubMed Web of Science ®Google Scholar
• Kim EM, Hwang O. Role of matrix metalloproteinase-3 in neurodegeneration. J Neurochem 2011; 116:22 - 32; http://dx.doi.org/10.1111/j.1471-4159.2010.07082.x; PMID: 21044079
   PubMed Web of Science ®Google Scholar
• Joo SH, Kwon KJ, Kim JW, Kim JW, Hasan MR, Lee HJ, et al. Regulation of matrix metalloproteinase-9 and tissue plasminogen activator activity by alpha-synuclein in rat primary glial cells. Neurosci Lett 2010; 469:352 - 6; http://dx.doi.org/10.1016/j.neulet.2009.12.026; PMID: 20026244
   PubMed Web of Science ®Google Scholar
• Kim S, Cho SH, Kim KY, Shin KY, Kim HS, Park CH, et al. Alpha-synuclein induces migration of BV-2 microglial cells by up-regulation of CD44 and MT1-MMP. J Neurochem 2009; 109:1483 - 96; http://dx.doi.org/10.1111/j.1471-4159.2009.06075.x; PMID: 19457162
   PubMed Web of Science ®Google Scholar
• Melchor JP, Pawlak R, Strickland S. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-beta (Abeta) degradation and inhibits Abeta-induced neurodegeneration. J Neurosci 2003; 23:8867 - 71; PMID: 14523088
   PubMed Web of Science ®Google Scholar
• Cacquevel M, Launay S, Castel H, Benchenane K, Chéenne S, Buée L, et al. Ageing and amyloid-beta peptide deposition contribute to an impaired brain tissue plasminogen activator activity by different mechanisms. Neurobiol Dis 2007; 27:164 - 73; http://dx.doi.org/10.1016/j.nbd.2007.04.004; PMID: 17566751
   PubMed Web of Science ®Google Scholar
• Sutton R, Keohane ME, VanderBerg SR, Gonias SL. Plasminogen activator inhibitor-1 in the cerebrospinal fluid as an index of neurological disease. Blood Coagul Fibrinolysis 1994; 5:167 - 71; http://dx.doi.org/10.1097/00001721-199404000-00002; PMID: 8054448
   PubMed Web of Science ®Google Scholar
• Kornblatt JA, Marchal S, Rezaei H, Kornblatt MJ, Balny C, Lange R, et al. The fate of the prion protein in the prion/plasminogen complex. Biochem Biophys Res Commun 2003; 305:518 - 22; http://dx.doi.org/10.1016/S0006-291X(03)00804-0; PMID: 12763023
   PubMed Web of Science ®Google Scholar
• Apelt J, Ach K, Schliebs R. Aging-related down-regulation of neprilysin, a putative beta-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of beta-amyloid plaques. Neurosci Lett 2003; 339:183 - 6; http://dx.doi.org/10.1016/S0304-3940(03)00030-2; PMID: 12633883
   PubMed Web of Science ®Google Scholar
• Ferretti MT, Partridge V, Leon WC, Canneva F, Allard S, Arvanitis DN, et al. Transgenic mice as a model of pre-clinical Alzheimer’s disease. Curr Alzheimer Res 2011; 8:4 - 23; http://dx.doi.org/10.2174/156720511794604561; PMID: 21143159
   PubMed Web of Science ®Google Scholar
• Nalivaevaa NN, Fisk L, Kochkina EG, Plesneva SA, Zhuravin IA, Babusikova E, et al. Effect of hypoxia/ischemia and hypoxic preconditioning/reperfusion on expression of some amyloid-degrading enzymes. Ann N Y Acad Sci 2004; 1035:21 - 33; http://dx.doi.org/10.1196/annals.1332.002; PMID: 15681798
   PubMed Web of Science ®Google Scholar
• Masliah E, Rockenstein E, Adame A, Alford M, Crews L, Hashimoto M, et al. Effects of alpha-synuclein immunization in a mouse model of Parkinson’s disease. Neuron 2005; 46:857 - 68; http://dx.doi.org/10.1016/j.neuron.2005.05.010; PMID: 15953415
   PubMed Web of Science ®Google Scholar
• Masliah E, Rockenstein E, Mante M, Crews L, Spencer B, Adame A, et al. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One 2011; 6:e19338; http://dx.doi.org/10.1371/journal.pone.0019338; PMID: 21559417
   PubMed Web of Science ®Google Scholar
• Danzer KM, Ruf WP, Putcha P, Joyner D, Hashimoto T, Glabe C, et al. Heat-shock protein 70 modulates toxic extracellular α-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J 2011; 25:326 - 36; http://dx.doi.org/10.1096/fj.10-164624; PMID: 20876215
   PubMed Web of Science ®Google Scholar
• Kurz A, Perneczky R. Amyloid clearance as a treatment target against Alzheimer’s disease. J Alzheimers Dis 2011; 24:Suppl 2 61 - 73; PMID: 21422524
   PubMedGoogle Scholar
• Sokolowski JD, Mandell JW. Phagocytic clearance in neurodegeneration. Am J Pathol 2011; 178:1416 - 28; http://dx.doi.org/10.1016/j.ajpath.2010.12.051; PMID: 21435432
   PubMed Web of Science ®Google Scholar
• Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy?. Nat Rev Neurol 2010; 6:108 - 19; http://dx.doi.org/10.1038/nrneurol.2009.219; PMID: 20140000
   PubMed Web of Science ®Google Scholar
• Sadowski MJ, Pankiewicz J, Prelli F, Scholtzova H, Spinner DS, Kascsak RB, et al. Anti-PrP Mab 6D11 suppresses PrP(Sc) replication in prion infected myeloid precursor line FDC-P1/22L and in the lymphoreticular system in vivo. Neurobiol Dis 2009; 34:267 - 78; http://dx.doi.org/10.1016/j.nbd.2009.01.013; PMID: 19385058
   PubMed Web of Science ®Google Scholar
• Götz J, Ittner A, Ittner LM. Tau-targeted treatment strategies in Alzheimer’s disease. Br J Pharmacol 2012; 165:1246 - 59; http://dx.doi.org/10.1111/j.1476-5381.2011.01713.x; PMID: 22044248
   PubMed Web of Science ®Google Scholar
• Gros-Louis F, Soucy G, Larivière R, Julien JP. Intracerebroventricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALS. J Neurochem 2010; 113:1188 - 99; PMID: 20345765
   PubMed Web of Science ®Google Scholar
• Urushitani M, Ezzi SA, Julien JP. Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2007; 104:2495 - 500; http://dx.doi.org/10.1073/pnas.0606201104; PMID: 17277077
   PubMed Web of Science ®Google Scholar