Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond

Journal of Cell Biology

Volumn 187, Issue 6, 2009, Pages 761-772

  Ilieva, Hristelina ^a   Polymenidou, Magdalini ^a   Cleveland, Don W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; GLUTAMIC ACID; SUPEROXIDE; SUPEROXIDE DISMUTASE;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; CELL TYPE; DEGENERATIVE DISEASE; DISEASE COURSE; EXCITOTOXICITY; HUMAN; HUNTINGTON CHOREA; INTERNEURON; MICROGLIA; MOTONEURON; MUTATION; NERVE CELL DEGENERATION; NERVE CELL LESION; NONHUMAN; PARKINSON DISEASE; PRION DISEASE; PRIORITY JOURNAL; REVIEW; SPINOCEREBELLAR DEGENERATION; TAUOPATHY; ANIMAL; CAPILLARY; CELL DEATH; ENDOPLASMIC RETICULUM; ENZYMOLOGY; GENETICS; METABOLISM; NERVE CELL; NERVE DEGENERATION; NERVE FIBER TRANSPORT; PATHOLOGY; PHYSIOLOGICAL STRESS; T LYMPHOCYTE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; ASTROCYTES; AXONAL TRANSPORT; CAPILLARIES; CELL DEATH; ENDOPLASMIC RETICULUM; GLUTAMIC ACID; HUMANS; MICROGLIA; MUTATION; NERVE DEGENERATION; NEURONS; STRESS, PHYSIOLOGICAL; SUPEROXIDE DISMUTASE; SUPEROXIDES; T-LYMPHOCYTES;

EID: 74049164709     PISSN: 00219525     EISSN: 00219525     Source Type: Journal    
DOI: 10.1083/jcb.200908164     Document Type: Review

References (115)

1. Aguzzi, A., and A.M. Calella. 2009. Prions: protein aggregation and infectious diseases. Physiol. Rev. 89:1105-1152. doi:10.1152/physrev. 00006.2009
2. Ajami, B., J.L. Bennett, C. Krieger, W. Tetzlaff, and F.M. Rossi. 2007. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10:1538-1543. doi:10.1038/nn2014
3. Basler, K., B. Oesch, M. Scott, D. Westaway, M. Wälchli, D.F. Groth, M.P. McKinley, S.B. Prusiner, and C. Weissmann. 1986. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell. 46:417-428. doi:10.1016/0092-8674(86)90662-8
4. Beers, D.R., J.S. Henkel, Q. Xiao, W. Zhao, J. Wang, A.A. Yen, L. Siklos, S.R. McKercher, and S.H. Appel. 2006. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA. 103:16021-16026. doi:10.1073/pnas.0607423103
5. Beers, D.R., J.S. Henkel, W. Zhao, J. Wang, and S.H. Appel. 2008. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc. Natl. Acad. Sci. USA. 105:15558-15563. doi:10.1073/pnas.0807419105
6. Boillée, S., K. Yamanaka, C.S. Lobsiger, N.G. Copeland, N.A. Jenkins, G. Kassiotis, G. Kollias, and D.W. Cleveland. 2006. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 312:1389-1392. doi:10.1126/science.1123511
7. Boston-Howes, W., S.L. Gibb, E.O. Williams, P. Pasinelli, R.H. Brown Jr., and D. Trotti. 2006. Caspase-3 cleaves and inactivates the glutamate transporter EAAT2. J. Biol. Chem. 281:14076-14084. doi:10.1074/jbc. M600653200
8. Brochard, V., B. Combadière, A. Prigent, Y. Laouar, A. Perrin, V. Beray-Berthat, O. Bonduelle, D. Alvarez-Fischer, J. Callebert, J.M. Launay, et al. 2009. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J. Clin. Invest. 119:182-192.
9. Browne, S.E., L. Yang, J.P. DiMauro, S.W. Fuller, S.C. Licata, and M.F. Beal. 2006. Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS. Neurobiol. Dis. 22:599-610. doi:10.1016/j.nbd.2006.01.001
10. Bruijn, L.I., M.W. Becher, M.K. Lee, K.L. Anderson, N.A. Jenkins, N.G. Copeland, S.S. Sisodia, J.D. Rothstein, D.R. Borchelt, D.L. Price, and D.W. Cleveland. 1997. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron. 18:327-338. doi:10.1016/S0896-6273(00)80272-X
11. Bruijn, L.I., M.K. Houseweart, S. Kato, K.L. Anderson, S.D. Anderson, E. Ohama, A.G. Reaume, R.W. Scott, and D.W. Cleveland. 1998. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science. 281:1851-1854. doi:10.1126/science.281.5384.1851
12. Büeler, H., A. Aguzzi, A. Sailer, R.A. Greiner, P. Autenried, M. Aguet, and C. Weissmann. 1993. Mice devoid of PrP are resistant to scrapie. Cell. 73:1339-1347. doi:10.1016/0092-8674(93)90360-3
13. Cairns, N.J., M. Neumann, E.H. Bigio, I.E. Holm, D. Troost, K.J. Hatanpaa, C. Foong, C.L. White III, J.A. Schneider, H.A. Kretzschmar, et al. 2007. TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am. J. Pathol. 171:227-240. doi:10.2353/ajpath. 2007.070182
14. Cassina, P., A. Cassina, M. Pehar, R. Castellanos, M. Gandelman, A. de León, K.M. Robinson, R.P. Mason, J.S. Beckman, L. Barbeito, and R. Radi. 2008. Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants. J. Neurosci. 28:4115-4122. doi:10.1523/ JNEUROSCI.5308-07.2008
15. Chen, M., V.O. Ona, M. Li, R.J. Ferrante, K.B. Fink, S. Zhu, J. Bian, L. Guo, L.A. Farrell, S.M. Hersch, et al. 2000. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat. Med. 6:797-801. doi:10.1038/80538
16. Chen, X.J., E.N. Levedakou, K.J. Millen, R.L. Wollmann, B. Soliven, and B. Popko. 2007. Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J. Neurosci. 27:14515-14524. doi:10.1523/JNEUROSCI.4338-07.2007
17. Cheroni, C., M. Marino, M. Tortarolo, P. Veglianese, S. De Biasi, E. Fontana, L.V. Zuccarello, C.J. Maynard, N.P. Dantuma, and C. Bendotti. 2009. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. Hum. Mol. Genet. 18:82-96. doi:10.1093/hmg/ddn319
18. Chesebro, B., M. Trifilo, R. Race, K. Meade-White, C. Teng, R. LaCasse, L. Raymond, C. Favara, G. Baron, S. Priola, et al. 2005. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science. 308:1435-1439. doi:10.1126/science.1110837
19. Chiu, I.M., A. Chen, Y. Zheng, B. Kosaras, S.A. Tsiftsoglou, T.K. Vartanian, R.H. Brown Jr., and M.C. Carroll. 2008. T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc. Natl. Acad. Sci. USA. 105:17913-17918. doi:10.1073/pnas.0804610105
20. Choi, D.K., S. Pennathur, C. Perier, K. Tieu, P. Teismann, D.C. Wu, V. Jackson-Lewis, M. Vila, J.P. Vonsattel, J.W. Heinecke, and S. Przedborski. 2005. Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson's disease in mice. J. Neurosci. 25:6594-6600. doi:10.1523/JNEUROSCI.0970-05.2005
21. Choi, S.H., K. Veeraraghavalu, O. Lazarov, S. Marler, R.M. Ransohoff, J.M. Ramirez, and S.S. Sisodia. 2008. Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron. 59:568-580. doi:10.1016/j.neuron.2008.07.033
22. Clement, A.M., M.D. Nguyen, E.A. Roberts, M.L. Garcia, S. Boillée, M. Rule, A.P. McMahon, W. Doucette, D. Siwek, R.J. Ferrante, et al. 2003. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science. 302:113-117. doi:10.1126/science.1086071
23. Custer, S.K., G.A. Garden, N. Gill, U. Rueb, R.T. Libby, C. Schultz, S.J. Guyenet, T. Deller, L.E. Westrum, B.L. Sopher, and A.R. La Spada. 2006. Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport. Nat. Neurosci. 9:1302-1311. doi:10.1038/nn1750
24. Damiano, M., A.A. Starkov, S. Petri, K. Kipiani, M. Kiaei, M. Mattiazzi, M. Flint Beal, and G. Manfredi. 2006. Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J. Neurochem. 96:1349-1361. doi:10.1111/j.1471- 4159.2006.03619.x
25. Dauer, W., and S. Przedborski. 2003. Parkinson's disease: mechanisms and models. Neuron. 39:889-909. doi:10.1016/S0896-6273(03)00568-3
26. Diedrich, J.F., P.E. Bendheim, Y.S. Kim, R.I. Carp, and A.T. Haase. 1991. Scrapie-associated prion protein accumulates in astrocytes during scrapie infection. Proc. Natl. Acad. Sci. USA. 88:375-379. doi:10.1073/pnas.88.2. 375
27. Dobrowolny, G., M. Aucello, E. Rizzuto, S. Beccafico, C. Mammucari, S. Boncompagni, S. Bonconpagni, S. Belia, F. Wannenes, C. Nicoletti, et al. 2008. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab. 8:425-436. doi:10.1016/j.cmet.2008.09.002
28. Ekblom, J., S.S. Jossan, M. Bergström, L. Oreland, E. Walum, and S.M. Aquilonius. 1993. Monoamine oxidase-B in astrocytes. Glia. 8:122-132. doi:10.1002/glia.440080208
29. Eklund, C.M., R.C. Kennedy, and W.J. Hadlow. 1967. Pathogenesis of scrapie virus infection in the mouse. J. Infect. Dis. 117:15-22.
30. Falsig, J., C. Julius, I. Margalith, P. Schwarz, F.L. Heppner, and A. Aguzzi. 2008. A versatile prion replication assay in organotypic brain slices. Nat. Neurosci. 11:109-117. doi:10.1038/nn2028
31. Forman, M.S., D. Lal, B. Zhang, D.V. Dabir, E. Swanson, V.M. Lee, and J.Q. Trojanowski. 2005. Transgenic mouse model of tau pathology in astro cytes leading to nervous system degeneration. J. Neurosci. 25:3539-3550. doi:10.1523/JNEUROSCI.0081-05.2005
32. Garden, G.A., R.T. Libby, Y.H. Fu, Y. Kinoshita, J. Huang, D.E. Possin, A.C. Smith, R.A. Martinez, G.C. Fine, S.K. Grote, et al. 2002. Polyglutamine-expanded ataxin-7 promotes non-cell-autonomous purkinje cell degeneration and displays proteolytic cleavage in ataxic transgenic mice. J. Neurosci. 22:4897-4905.
33. Gong, Y.H., A.S. Parsadanian, A. Andreeva, W.D. Snider, and J.L. Elliott. 2000. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J. Neurosci. 20:660-665.
34. Gowing, G., T. Philips, B. Van Wijmeersch, J.N. Audet, M. Dewil, L. Van Den Bosch, A.D. Billiau, W. Robberecht, and J.P. Julien. 2008. Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J. Neurosci. 28:10234-10244. doi:10.1523/JNEUROSCI.3494-08.2008
35. Gu, X., C. Li, W. Wei, V. Lo, S. Gong, S.H. Li, T. Iwasato, S. Itohara, X.J. Li, I. Mody, et al. 2005. Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice. Neuron. 46:433-444. doi:10.1016/j.neuron.2005.03.025
36. Gu, X., V.M. André, C. Cepeda, S.H. Li, X.J. Li, M.S. Levine, and X.W. Yang. 2007. Pathological cell-cell interactions are necessary for striatal pathogenesis in a conditional mouse model of Huntington's disease. Mol. Neurodegener. 2:8. doi:10.1186/1750-1326-2-8
37. Hardy, J., P. Lewis, T. Revesz, A. Lees, and C. Paisan-Ruiz. 2009. The genetics of Parkinson's syndromes: a critical review. Curr. Opin. Genet. Dev. 19:254-265. doi:10.1016/j.gde.2009.03.008
38. Harold, D., R. Abraham, P. Hollingworth, R. Sims, A. Gerrish, M.L. Hamshere, J.S. Pahwa, V. Moskvina, K. Dowzell, A. Williams, et al. 2009. Genomewide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat. Genet. 41:1088-1093. doi:10.1038/ng.440
39. Harraz, M.M., J.J. Marden, W. Zhou, Y. Zhang, A. Williams, V.S. Sharov, K. Nelson, M. Luo, H. Paulson, C. Schöneich, and J.F. Engelhardt. 2008. SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J. Clin. Invest. 118:659-670.
40. Henkel, J.S., D.R. Beers, S. Wen, R. Bowser, and S.H. Appel. 2009. Decreased mRNA expression of tight junction proteins in lumbar spinal cords of patients with ALS. Neurology. 72:1614-1616. doi:10.1212/WNL. 0b013e3181a41228
41. Hoffman, E.K., H.M. Wilcox, R.W. Scott, and R. Siman. 1996. Proteasome inhibition enhances the stability of mouse Cu/Zn superoxide dismutase with mutations linked to familial amyotrophic lateral sclerosis. J. Neurol. Sci. 139:15-20. doi:10.1016/S0022-510X(96)00031-7
42. Holzbaur, E.L., D.S. Howland, N. Weber, K. Wallace, Y. She, S. Kwak, L.A. Tchistiakova, E. Murphy, J. Hinson, R. Karim, et al. 2006. Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis. Neurobiol. Dis. 23:697-707. doi:10.1016/j.nbd.2006.05.009
43. Howland, D.S., J. Liu, Y. She, B. Goad, N.J. Maragakis, B. Kim, J. Erickson, J. Kulik, L. DeVito, G. Psaltis, et al. 2002. Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc. Natl. Acad. Sci. USA. 99:1604-1609. doi:10.1073/pnas.032539299
44. Hunot, S., M. Vila, P. Teismann, R.J. Davis, E.C. Hirsch, S. Przedborski, P. Rakic, and R.A. Flavell. 2004. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. USA. 101:665-670. doi:10.1073/pnas.0307453101
45. Ii, K., H. Ito, K. Tanaka, and A. Hirano. 1997. Immunocytochemical colocalization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly. J. Neuropathol. Exp. Neurol. 56:125-131. doi:10.1097/00005072-199702000-00002
46. Ilieva, H.S., K. Yamanaka, S. Malkmus, O. Kakinohana, T. Yaksh, M. Marsala, and D.W. Cleveland. 2008. Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death. Proc. Natl. Acad. Sci. USA. 105:12599-12604. doi:10.1073/pnas.0805422105
47. Jaarsma, D., E. Teuling, E.D. Haasdijk, C.I. De Zeeuw, and C.C. Hoogenraad. 2008. Neuron-specific expression of mutant superoxide dismutase is sufficient to induce amyotrophic lateral sclerosis in transgenic mice. J. Neurosci. 28:2075-2088. doi:10.1523/JNEUROSCI.5258-07.2008
48. Jahng, J.W., T.A. Houpt, T.C. Wessel, K. Chen, J.C. Shih, and T.H. Joh. 1997. Localization of monoamine oxidase A and B mRNA in the rat brain by in situ hybridization. Synapse. 25:30-36. doi:10.1002/(SICI)1098-2396(199701)25: 1〈30::AID-SYN4〉3.0.CO;2-G
49. Jeffrey, M., C.M. Goodsir, R.E. Race, and B. Chesebro. 2004. Scrapie-specific neuronal lesions are independent of neuronal PrP expression. Ann. Neurol. 55:781-792. doi:10.1002/ana.20093
50. Kabashi, E., J.N. Agar, D.M. Taylor, S. Minotti, and H.D. Durham. 2004. Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis. J. Neurochem. 89:1325-1335. doi:10.1111/j.1471-4159.2004.02453.x
51. Kang, J., and S. Rivest. 2007. MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis. J. Cell Biol. 179:1219-1230. doi:10.1083/jcb.200705046
52. Kikuchi, H., G. Almer, S. Yamashita, C. Guégan, M. Nagai, Z. Xu, A.A. Sosunov, G.M. McKhann II, and S. Przedborski. 2006. Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model. Proc. Natl. Acad. Sci. USA. 103:6025-6030. doi:10.1073/pnas.0509227103
53. Kitahama, K., R.M. Denney, T. Maeda, and M. Jouvet. 1991. Distribution of type B monoamine oxidase immunoreactivity in the cat brain with reference to enzyme histochemistry. Neuroscience. 44:185-204. doi:10.1016/0306- 4522(91)90260-U
54. Kwiatkowski, T.J. Jr., D.A. Bosco, A.L. Leclerc, E. Tamrazian, C.R. Vanderburg, C. Russ, A. Davis, J. Gilchrist, E.J. Kasarskis, T. Munsat, et al. 2009. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 323:1205-1208. doi:10.1126/science.1166066
55. Lambert, J.C., S. Heath, G. Even, D. Campion, K. Sleegers, M. Hiltunen, O. Combarros, D. Zelenika, M.J. Bullido, B. Tavernier, et al; European Alzheimer's Disease Initiative Investigators. 2009. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat. Genet. 41:1094-1099. doi:10.1038/ng.439
56. Lepore, A.C., B. Rauck, C. Dejea, A.C. Pardo, M.S. Rao, J.D. Rothstein, and N.J. Maragakis. 2008. Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat. Neurosci. 11:1294-1301. doi:10.1038/nn.2210
57. Liberatore, G.T., V. Jackson-Lewis, S. Vukosavic, A.S. Mandir, M. Vila, W.G. McAuliffe, V.L. Dawson, T.M. Dawson, and S. Przedborski. 1999. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat. Med. 5:1403-1409. doi:10.1038/70978
58. Lino, M.M., C. Schneider, and P. Caroni. 2002. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J. Neurosci. 22:4825-4832.
59. Liu, J., C. Lillo, P.A. Jonsson, C. Vande Velde, C.M. Ward, T.M. Miller, J.R. Subramaniam, J.D. Rothstein, S. Marklund, P.M. Andersen, et al. 2004. Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron. 43:5-17. doi:10.1016/j.neuron.2004.06.016
60. Lobsiger, C.S., S. Boillee, M. McAlonis-Downes, A.M. Khan, M.L. Feltri, K. Yamanaka, and D.W. Cleveland. 2009. Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc. Natl. Acad. Sci. USA. 106:4465-4470. doi:10.1073/pnas.0813339106
61. Luque, J.M., S.W. Kwan, C.W. Abell, M. Da Prada, and J.G. Richards. 1995. Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system. J. Comp. Neurol. 363:665-680. doi:10.1002/cne.903630410
62. Mallucci, G., A. Dickinson, J. Linehan, P.C. Klöhn, S. Brandner, and J. Collinge. 2003. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science. 302:871-874.
63. Marszalek, J.R., T.L. Williamson, M.K. Lee, Z. Xu, P.N. Hoffman, M.W. Becher, T.O. Crawford, and D.W. Cleveland. 1996. Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport. J. Cell Biol. 135:711-724. doi:10.1083/jcb.135.3.711
64. Masliah, E., E. Rockenstein, I. Veinbergs, M. Mallory, M. Hashimoto, A. Takeda, Y. Sagara, A. Sisk, and L. Mucke. 2000. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science. 287:1265-1269. doi:10.1126/science.287.5456.1265
65. Mattiazzi, M., M. D'Aurelio, C.D. Gajewski, K. Martushova, M. Kiaei, M.F. Beal, and G. Manfredi. 2002. Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J. Biol. Chem. 277:29626-29633. doi:10.1074/jbc.M203065200
66. Mildner, A., H. Schmidt, M. Nitsche, D. Merkler, U.K. Hanisch, M. Mack, M. Heikenwalder, W. Brück, J. Priller, and M. Prinz. 2007. Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat. Neurosci. 10:1544-1553. doi:10.1038/nn2015
67. Miller, T.M., S.H. Kim, K. Yamanaka, M. Hester, P. Umapathi, H. Arnson, L. Rizo, J.R. Mendell, F.H. Gage, D.W. Cleveland, and B.K. Kaspar. 2006. Gene transfer demonstrates that muscle is not a primary target for noncell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA. 103:19546-19551. doi:10.1073/pnas.0609411103
68. Murakami, T., I. Nagano, T. Hayashi, Y. Manabe, M. Shoji, Y. Setoguchi, and K. Abe. 2001. Impaired retrograde axonal transport of adenovirus-mediated E. coli LacZ gene in the mice carrying mutant SOD1 gene. Neurosci. Lett. 308:149-152. doi:10.1016/S0304-3940(01)02036-5
69. Nakamura, S., T. Kawamata, I. Akiguchi, M. Kameyama, N. Nakamura, and H. Kimura. 1990. Expression of monoamine oxidase B activity in astrocytes of senile plaques. Acta Neuropathol. 80:419-425. doi:10.1007/BF00307697
70. Neumann, M., D.M. Sampathu, L.K. Kwong, A.C. Truax, M.C. Micsenyi, T.T. Chou, J. Bruce, T. Schuck, M. Grossman, C.M. Clark, et al. 2006. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 314:130-133. doi:10.1126/science.1134108
71. Nishitoh, H., H. Kadowaki, A. Nagai, T. Maruyama, T. Yokota, H. Fukutomi, T. Noguchi, A. Matsuzawa, K. Takeda, and H. Ichijo. 2008. ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev. 22:1451-1464. doi:10.1101/gad.1640108
72. Niwa, J., S. Ishigaki, N. Hishikawa, M. Yamamoto, M. Doyu, S. Murata, K. Tanaka, N. Taniguchi, and G. Sobue. 2002. Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity. J. Biol. Chem. 277:36793-36798. doi:10.1074/jbc.M206559200
73. Nuvolone, M., A. Aguzzi, and M. Heikenwalder. 2009. Cells and prions: a license to replicate. FEBS Lett. 583:2674-2684. doi:10.1016/j.febslet. 2009.06.014
74. Perlson, E., G.B. Jeong, J.L. Ross, R. Dixit, K.E. Wallace, R.G. Kalb, and E.L. Holzbaur. 2009. A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. J. Neurosci. 29:9903-9917. doi:10.1523/JNEUROSCI.0813-09.2009
75. Pramatarova, A., J. Laganière, J. Roussel, K. Brisebois, and G.A. Rouleau. 2001. Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J. Neurosci. 21:3369-3374.
76. Prinz, M., F. Montrasio, H. Furukawa, M.E. van der Haar, P. Schwarz, T. Rülicke, O.T. Giger, K.G. Häusler, D. Perez, M. Glatzel, and A. Aguzzi. 2004. Intrinsic resistance of oligodendrocytes to prion infection. J. Neurosci. 24:5974-5981. doi:10.1523/JNEUROSCI.0122-04.2004
77. Prusiner, S.B. 1982. Novel proteinaceous infectious particles cause scrapie. Science. 216:136-144. doi:10.1126/science.6801762
78. Puls, I., C. Jonnakuty, B.H. LaMonte, E.L. Holzbaur, M. Tokito, E. Mann, M.K. Floeter, K. Bidus, D. Drayna, S.J. Oh, et al. 2003. Mutant dynactin in motor neuron disease. Nat. Genet. 33:455-456. doi:10.1038/ng1123
79. Pun, S., A.F. Santos, S. Saxena, L. Xu, and P. Caroni. 2006. Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Nat. Neurosci. 9:408-419. doi:10.1038/nn1653
80. Raeber, A.J., R.E. Race, S. Brandner, S.A. Priola, A. Sailer, R.A. Bessen, L. Mucke, J. Manson, A. Aguzzi, M.B. Oldstone, et al. 1997. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J. 16:6057-6065. doi:10.1093/emboj/16.20.6057
81. Ralph, G.S., P.A. Radcliffe, D.M. Day, J.M. Carthy, M.A. Leroux, D.C. Lee, L.F. Wong, L.G. Bilsland, L. Greensmith, S.M. Kingsman, et al. 2005. Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nat. Med. 11:429-433. doi:10.1038/nm1205
82. Rosen, D.R., T. Siddique, D. Patterson, D.A. Figlewicz, P. Sapp, A. Hentati, D. Donaldson, J. Goto, J.P. O'Regan, H.X. Deng, et al. 1993. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 362:59-62. doi:10.1038/362059a0
83. Rothstein, J.D., M. Van Kammen, A.I. Levey, L.J. Martin, and R.W. Kuncl. 1995. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol. 38:73-84. doi:10.1002/ana.410380114
84. Sapp, E., K.B. Kegel, N. Aronin, T. Hashikawa, Y. Uchiyama, K. Tohyama, P.G. Bhide, J.P. Vonsattel, and M. DiFiglia. 2001. Early and progressive accumulation of reactive microglia in the Huntington disease brain. J. Neuropathol. Exp. Neurol. 60:161-172.
85. Saxena, S., E. Cabuy, and P. Caroni. 2009. A role for motoneuron subtypeselective ER stress in disease manifestations of FALS mice. Nat. Neurosci. 12:627-636. doi:10.1038/nn.2297
86. Shin, J.Y., Z.H. Fang, Z.X. Yu, C.E. Wang, S.H. Li, and X.J. Li. 2005. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J. Cell Biol. 171:1001-1012. doi:10.1083/jcb.200508072
87. Sreedharan, J., I.P. Blair, V.B. Tripathi, X. Hu, C. Vance, B. Rogelj, S. Ackerley, J.C. Durnall, K.L. Williams, E. Buratti, et al. 2008. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 319:1668-1672. doi:10.1126/science.1154584
88. Streit, W.J., H. Braak, Q.S. Xue, and I. Bechmann. 2009. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathol. 118:475-485. doi:10.1007/s00401-009-0556-6
89. Tamgüney, G., M.W. Miller, L.L. Wolfe, T.M. Sirochman, D.V. Glidden, C. Palmer, A. Lemus, S.J. DeArmond, and S.B. Prusiner. 2009. Asymptomatic deer excrete infectious prions in faeces. Nature. 461:529-532. doi:10.1038/nature08289
90. Taroni, F., and S. DiDonato. 2004. Pathways to motor incoordination: the inherited ataxias. Nat. Rev. Neurosci. 5:641-655. doi:10.1038/nrn1474
91. Teismann, P., K. Tieu, D.K. Choi, D.C. Wu, A. Naini, S. Hunot, M. Vila, V. Jackson-Lewis, and S. Przedborski. 2003. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc. Natl. Acad. Sci. USA. 100:5473-5478. doi:10.1073/pnas.0837397100
92. Towne, C., C. Raoul, B.L. Schneider, and P. Aebischer. 2008. Systemic AAV6 delivery mediating RNA interference against SOD1: neuromuscular transduction does not alter disease progression in fALS mice. Mol. Ther. 16:1018-1025. doi:10.1038/mt.2008.73
93. Turner, B.J., and K. Talbot. 2008. Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog. Neurobiol. 85:94-134. doi:10.1016/j.pneurobio.2008.01.001
94. Urushitani, M., J. Kurisu, K. Tsukita, and R. Takahashi. 2002. Proteasomal inhibition by misfolded mutant superoxide dismutase 1 induces selective motor neuron death in familial amyotrophic lateral sclerosis. J. Neurochem. 83:1030-1042. doi:10.1046/j.1471-4159.2002.01211.x
95. Urushitani, M., A. Sik, T. Sakurai, N. Nukina, R. Takahashi, and J.P. Julien. 2006. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat. Neurosci. 9:108-118. doi:10.1038/nn1603
96. Van Damme, P., E. Bogaert, M. Dewil, N. Hersmus, D. Kiraly, W. Scheveneels, I. Bockx, D. Braeken, N. Verpoorten, K. Verhoeven, et al. 2007. Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity. Proc. Natl. Acad. Sci. USA. 104:14825-14830. doi:10.1073/pnas.0705046104
97. Van Deerlin, V.M., J.B. Leverenz, L.M. Bekris, T.D. Bird, W. Yuan, L.B. Elman, D. Clay, E.M. Wood, A.S. Chen-Plotkin, M. Martinez-Lage, et al. 2008. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 7:409-416. doi:10.1016/S1474-4422(08)70071-1
98. Vance, C., B. Rogelj, T. Hortobágyi, K.J. De Vos, A.L. Nishimura, J. Sreedharan, X. Hu, B. Smith, D. Ruddy, P. Wright, et al. 2009. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 323:1208-1211. doi:10.1126/science.1165942
99. Vande Velde, C., T.M. Miller, N.R. Cashman, and D.W. Cleveland. 2008. Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria. Proc. Natl. Acad. Sci. USA. 105:4022-4027. doi:10.1073/pnas.0712209105
100. Vargas, M.R., D.A. Johnson, D.W. Sirkis, A. Messing, and J.A. Johnson. 2008. Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J. Neurosci. 28:13574-13581. doi:10.1523/JNEUROSCI.4099-08.2008
101. Vijayvergiya, C., M.F. Beal, J. Buck, and G. Manfredi. 2005. Mutant superoxide dismutase 1 forms aggregates in the brain mitochondrial matrix of amyotrophic lateral sclerosis mice. J. Neurosci. 25:2463-2470. doi:10.1523/JNEUROSCI.4385-04.2005
102. Wang, L., K. Sharma, G. Grisotti, and R.P. Roos. 2009. The effect of mutant SOD1 dismutase activity on non-cell autonomous degeneration in familial amyotrophic lateral sclerosis. Neurobiol. Dis. 35:234-240. doi:10.1016/j.nbd.2009.05.002
103. Watanabe, M., M. Dykes-Hoberg, V.C. Culotta, D.L. Price, P.C. Wong, and J.D. Rothstein. 2001. Histological evidence of protein aggregation in mutant SOD1 transgenic mice and in amyotrophic lateral sclerosis neural tissues. Neurobiol. Dis. 8:933-941. doi:10.1006/nbdi.2001.0443
104. Wegorzewska, I., S. Bell, N.J. Cairns, T.M. Miller, and R.H. Baloh. 2009. TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc. Natl. Acad. Sci. USA.
105. Williamson, T.L., and D.W. Cleveland. 1999. Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat. Neurosci. 2:50-56. doi:10.1038/4553
106. Wu, D.C., V. Jackson-Lewis, M. Vila, K. Tieu, P. Teismann, C. Vadseth, D.K. Choi, H. Ischiropoulos, and S. Przedborski. 2002. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine mouse model of Parkinson disease. J. Neurosci. 22:1763-1771.
107. Yamanaka, K., S. Boillee, E.A. Roberts, M.L. Garcia, M. McAlonis-Downes, O.R. Mikse, D.W. Cleveland, and L.S. Goldstein. 2008a. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc. Natl. Acad. Sci. USA. 105:7594-7599. doi:10.1073/pnas. 0802556105
108. Yamanaka, K., S.J. Chun, S. Boillee, N. Fujimori-Tonou, H. Yamashita, D.H. Gutmann, R. Takahashi, H. Misawa, and D.W. Cleveland. 2008b. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci. 11:251-253. doi:10.1038/nn2047
109. Yang, Y., O. Gozen, S. Vidensky, M.B. Robinson, and J.D. Rothstein. 2009a. Epigenetic regulation of neuron-dependent induction of astroglial synaptic protein GLT1. Glia.
110. Yang, Y., O. Gozen, A. Watkins, I. Lorenzini, A. Lepore, Y. Gao, S. Vidensky, J. Brennan, D. Poulsen, J. Won Park, et al. 2009b. Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron. 61:880-894. doi:10.1016/j.neuron.2009.02.010
111. Yazawa, I., B.I. Giasson, R. Sasaki, B. Zhang, S. Joyce, K. Uryu, J.Q. Trojanowski, and V.M. Lee. 2005. Mouse model of multiple system atrophy alphasynuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron. 45:847-859. doi:10.1016/j.neuron.2005.01.032
112. Zhao, W., D.R. Beers, J.S. Henkel, W. Zhang, M. Urushitani, J.P. Julien, and S.H. Appel. 2009. Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia. 58:231-243. doi:10.1002/glia.20919
113. Zhong, Z., R. Deane, Z. Ali, M. Parisi, Y. Shapovalov, M.K. O'Banion, K. Stojanovic, A. Sagare, S. Boillee, D.W. Cleveland, and B.V. Zlokovic. 2008. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat. Neurosci. 11:420-422. doi:10.1038/nn2073
114. Zhong, Z., H. Ilieva, L. Hallagan, R. Bell, I. Singh, N. Paquette, M. Thiyagarajan, R. Deane, J.A. Fernandez, S. Lane, et al. 2009. Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells. J. Clin. Invest. 119:3437-3449. doi:10.1172/JCI38476
115. Zoghbi, H.Y., and H.T. Orr. 2000. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23:217-247. doi:10.1146/annurev. neuro.23.1.217