Attenuation of AD-like neuropathology by harnessing peripheral immune cells: Local elevation of IL-10 and MMP-9

Journal of Neurochemistry

Volumn 111, Issue 6, 2009, Pages 1409-1424

  Koronyo Hamaoui, Maya ^a   Ko, Minhee K ^a,b   Koronyo, Yosef ^a   Azoulay, David ^a   Seksenyan, Akop ^a   Kunis, Gilad ^c   Pham, Michael ^a   Bakhsheshian, Joshua ^a   Rogeri, Patricia ^a   Black, Keith L ^a   Farkas, Daniel L ^a   Schwartz, Michal ^c  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Anti inflammatory; Glial scar; Matrix metalloproteinases; Monocytes; Neurodegeneration; Vaccination

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; CD45 ANTIGEN; CHONDROITIN SULFATE; GELATINASE B; INTERLEUKIN 10; PEPTIDE DERIVATIVE; PRESENILIN 1; PROTEIN MOG45D; PROTEOGLYCAN; SOMATOMEDIN C; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; ASTROCYTOSIS; CONTROLLED STUDY; DENDRITIC CELL; IMMUNIZATION; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; IMMUNOTHERAPY; INNATE IMMUNITY; MACROPHAGE; MICROGLIA; MOUSE; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE; TREATMENT RESPONSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; DENDRITIC CELLS; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; GLYCOPROTEINS; HUMANS; INSULIN-LIKE GROWTH FACTOR I; INTERLEUKIN-10; MALE; MATRIX METALLOPROTEINASE 9; MICE; MICE, TRANSGENIC; MUTATION; PEPTIDE FRAGMENTS; PRESENILIN-1; PROTEOCHONDROITIN SULFATES; TRANSFORMING GROWTH FACTOR BETA;

MUS MUSCULUS;

EID: 70450215332     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2009.06402.x     Document Type: Article

References (105)

1. Aguado-Llera D., Arilla-Ferreiro E., Campos-Barros A., Puebla-Jimenez L. Barrios V. (2005) Protective effects of insulin-like growth factor-I on the somatostatinergic system in the temporal cortex of beta-amyloid-treated rats. J. Neurochem. 92, 607 615.
2. Akiyama H., Barger S., Barnum S. et al. (2000) Inflammation and Alzheimer's disease. Neurobiol. Aging 21, 383 421.
3. Alkam T., Nitta A., Mizoguchi H., Saito K., Seshima M., Itoh A., Yamada K. Nabeshima T. (2008) Restraining tumor necrosis factor-alpha by thalidomide prevents the amyloid beta-induced impairment of recognition memory in mice. Behav. Brain Res. 189, 100 106.
4. Backstrom J. R., Lim G. P., Cullen M. J. Tokes Z. A. (1996) 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. 16, 7910 7919.
5. Bakalash S., Kipnis J., Yoles E. Schwartz M. (2002) Resistance of retinal ganglion cells to an increase in intraocular pressure is immune-dependent. Invest. Ophthalmol. Vis. Sci. 43, 2648 2653.
6. Bakalash S., Shlomo G. B., Aloni E., Shaked I., Wheeler L., Ofri R. Schwartz M. (2005) T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure. J. Mol. Med. 83, 904 916.
7. Banerjee R., Mosley R. L., Reynolds A. D., Dhar A., Jackson-Lewis V., Gordon P. H., Przedborski S. Gendelman H. E. (2008) Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice. PLoS ONE 3, e2740.
8. Brionne T. C., Tesseur I., Masliah E. Wyss-Coray T. (2003) Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 40, 1133 1145.
9. Butovsky O., Koronyo-Hamaoui M., Kunis G., Ophir E., Landa G., Cohen H. Schwartz M. (2006) Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc. Natl Acad. Sci. USA 103, 11784 11789.
10. Butovsky O., Kunis G., Koronyo-Hamaoui M. Schwartz M. (2007) Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model. Eur. J. Neurosci. 26, 413 416.
11. Cao C., Arendash G. W., Dickson A., Mamcarz M. B., Lin X. Ethell D. W. (2009) Abeta-specific Th2 cells provide cognitive and pathological benefits to Alzheimer's mice without infiltrating the CNS. Neurobiol. Dis. 34, 63 70.
12. Chiba T., Yamada M., Sasabe J., Terashita K., Shimoda M., Matsuoka M. Aiso S. (2008) Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons. Mol. Psychiatry 14, 206 222.
13. Deb S., Wenjun Zhang J. Gottschall P. E. (2003) Beta-amyloid induces the production of active, matrix-degrading proteases in cultured rat astrocytes. Brain Res. 970, 205 213.
14. DeWitt D. A., Silver J., Canning D. R. Perry G. (1993) Chondroitin sulfate proteoglycans are associated with the lesions of Alzheimer's disease. Exp. Neurol. 121, 149 152.
15. El Khoury J. Luster A. D. (2008) Mechanisms of microglia accumulation in Alzheimer's disease: therapeutic implications. Trends Pharmacol. Sci. 29, 626 632.
16. El Khoury J., Toft M., Hickman S. E., Means T. K., Terada K., Geula C. Luster A. D. (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat. Med. 13, 432 438.
17. Fawcett J. W. Asher R. A. (1999) The glial scar and central nervous system repair. Brain Res. Bull. 49, 377 391.
18. Ferguson T. A. Muir D. (2000) MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal laminae and are upregulated in degenerated nerve. Mol. Cell. Neurosci. 16, 157 167.
19. Fiala M., Cribbs D. H., Rosenthal M. Bernard G. (2007) Phagocytosis of amyloid-beta and inflammation: two faces of innate immunity in Alzheimer's disease. J. Alzheimer's Dis. 11, 457 463.
20. Fisher J., Levkovitch-Verbin H., Schori H., Yoles E., Butovsky O., Kaye J. F., Ben-Nun A. Schwartz M. (2001) Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies. J. Neurosci. 21, 136 142.
21. Ford A. L., Goodsall A. L., Hickey W. F. Sedgwick J. D. (1995) Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J. Immunol. 154, 4309 4321.
22. Ford A. L., Foulcher E., Lemckert F. A. Sedgwick J. D. (1996) Microglia induce CD4 T lymphocyte final effector function and death. J. Exp. Med. 184, 1737 1745.
23. Frenkel D., Huang Z., Maron R., Koldzic D. N., Moskowitz M. A. Weiner H. L. (2005a) Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke. J. Neurol. Sci. 233, 125 132.
24. Frenkel D., Maron R., Burt D. S. Weiner H. L. (2005b) Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease. J. Clin. Invest. 115, 2423 2433.
25. Garcia-Alloza M., Borrelli L. A., Rozkalne A., Hyman B. T. Bacskai B. J. (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J. Neurochem. 102, 1095 1104.
26. Gasparini L. Xu H. (2003) Potential roles of insulin and IGF-1 in Alzheimer's disease. Trends Neurosci. 26, 404 406.
27. Glenner G. G., Wong C. W., Quaranta V. Eanes E. D. (1984) The amyloid deposits in Alzheimer's disease: their nature and pathogenesis. Appl. Pathol. 2, 357 369.
28. Gottschall P. E. Deb S. (1996) Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. Neuroimmunomodulation 3, 69 75.
29. Hampel H., Teipel S. J., Fuchsberger T. et al. (2004) Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Mol. Psychiatry 9, 705 710.
30. Hardy J. Selkoe D. J. (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353 356.
31. Hauben E., Butovsky O., Nevo U. et al. (2000a) Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J. Neurosci. 20, 6421 6430.
32. Hauben E., Nevo U., Yoles E. et al. (2000b) Autoimmune T cells as potential neuroprotective therapy for spinal cord injury. Lancet 355, 286 287.
33. Hauben E., Agranov E., Gothilf A., Nevo U., Cohen A., Smirnov I., Steinman L. Schwartz M. (2001) Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease. J. Clin. Invest. 108, 591 599.
34. Hauben E., Gothilf A., Cohen A., Butovsky O., Nevo U., Smirnov I., Yoles E., Akselrod S. Schwartz M. (2003) Vaccination with dendritic cells pulsed with peptides of myelin basic protein promotes functional recovery from spinal cord injury. J. Neurosci. 23, 8808 8819.
35. Hawkes C. A. McLaurin J. (2009) Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc. Natl Acad. Sci. USA 106, 1261 1266.
36. He J. Crews F. T. (2007) Neurogenesis decreases during brain maturation from adolescence to adulthood. Pharmacol. Biochem. Behav. 86, 327 333.
37. Hermes G., Ajioka J. W., Kelly K. A. et al. (2008) Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. J. Neuroinflammation 5, 48.
38. Jankowsky J. L., Fadale D. J., Anderson J. et al. (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13, 159 170.
39. Jarvis K., Assis-Nascimento P., Mudd L. M. Montague J. R. (2007) Beta-amyloid toxicity and reversal in embryonic rat septal neurons. Neurosci. Lett. 423, 184 188. (Pubitemid 47285476)
40. Juedes A. E. Ruddle N. H. (2001) Resident and infiltrating central nervous system APCs regulate the emergence and resolution of experimental autoimmune encephalomyelitis. J. Immunol. 166, 5168 5175.
41. Juedes A. E., Hjelmstrom P., Bergman C. M., Neild A. L. Ruddle N. H. (2000) Kinetics and cellular origin of cytokines in the central nervous system: insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J. Immunol. 164, 419 426.
42. Kipnis J., Yoles E., Porat Z., Cohen A., Mor F., Sela M., Cohen I. R. Schwartz M. (2000) T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc. Natl Acad. Sci. USA 97, 7446 7451.
43. Koehler N. K., Genain C. P., Giesser B. Hauser S. L. (2002) The human T cell response to myelin oligodendrocyte glycoprotein: a multiple sclerosis family-based study. J. Immunol. 168, 5920 5927.
44. Koffie R. M., Meyer-Luehmann M., Hashimoto T. et al. (2009) Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc. Natl Acad. Sci. USA 106, 4012 4017.
45. Lauren J., Gimbel D. A., Nygaard H. B., Gilbert J. W. Strittmatter S. M. (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457, 1128 1132.
46. Lefterov I., Fitz N. F., Cronican A., Lefterov P., Staufenbiel M. Koldamova R. (2009) Memory deficits in APP23/Abca1+/- mice correlate with the level of Abeta oligomers. ASN Neuro 1, e00006, doi :.
47. Lewitus G. M. Schwartz M. (2008) Behavioral immunization: immunity to self-antigens contributes to psychological stress resilience. Mol. Psychiatry 14, 532 536.
48. Lewitus G. M., Ziv A. W., Gersner M. S., Zangen A. Schwartz M. (2008) Vaccination as a Novel Approach for Treating Depressive Behavior. Biol. Psychiatry 65, 283 288.
49. Li S., Hong S., Shepardson N. E., Walsh D. M., Shankar G. M. Selkoe D. (2009) Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62, 788 801.
50. Liesz A., Suri-Payer E., Veltkamp C., Doerr H., Sommer C., Rivest S., Giese T. Veltkamp R. (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med. 15, 192 199.
51. Lutz M. B. Schuler G. (2002) Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 23, 445 449.
52. Masters C. L., Wyss-Coray T. Pasinetti G. M. (2008) Anti-inflammatory drugs fall short in Alzheimer's disease. Nat. Med. 14, 916.
53. Matsui F. Oohira A. (2004) Proteoglycans and injury of the central nervous system. Congenit. Anom. (Kyoto) 44, 181 188.
54. McKeon R. J., Jurynec M. J. Buck C. R. (1999) The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J. Neurosci. 19, 10778 10788.
55. Mentlein R., Ludwig R. Martensen I. (1998) Proteolytic degradation of Alzheimer's disease amyloid beta-peptide by a metalloproteinase from microglia cells. J. Neurochem. 70, 721 726.
56. Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I. R. Schwartz M. (1999) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5, 49 55.
57. Moreno H., Yu E., Pigino G., Hernandez A. I., Kim N., Moreira J. E., Sugimori M. Llinas R. R. (2009) Synaptic transmission block by presynaptic injection of oligomeric amyloid beta. Proc. Natl Acad. Sci. USA 106, 5901 5906.
58. Nakamura H., Fujii Y., Inoki I., Sugimoto K., Tanzawa K., Matsuki H., Miura R., Yamaguchi Y. Okada Y. (2000) Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites. J. Biol. Chem. 275, 38885 38890.
59. Nalivaeva N. N., Fisk L. R., Belyaev N. D. Turner A. J. (2008) Amyloid-degrading enzymes as therapeutic targets in Alzheimer's disease. Curr. Alzheimer Res. 5, 212 224.
60. Olsson T., Diener P., Ljungdahl A., Hojeberg B., van der Meide P. H. Kristensson K. (1992) Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus. Autoimmunity 13, 117 126.
61. Price D. L., Whitehouse P. J. Struble R. G. (1985) Alzheimer's disease. Annu. Rev. Med. 36, 349 356.
62. Rapalino O., Lazarov-Spiegler O., Agranov E. et al. (1998) Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat. Med. 4, 814 821.
63. Renno T., Krakowski M., Piccirillo C., Lin J. Y. Owens T. (1995) TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines. J. Immunol. 154, 944 953.
64. Rolls A., Shechter R., London A., Segev Y., Jacob-Hirsch J., Amariglio N., Rechavi G. Schwartz M. (2008) Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med. 5, e171.
65. Rolls A., Shechter R. Schwartz M. (2009) The bright side of the glial scar in CNS repair. Nat. Rev. Neurosci. 10, 235 241.
66. Ryu E. K., Choe Y. S., Lee K. H., Choi Y. Kim B. T. (2006) Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J. Med. Chem. 49, 6111 6119.
67. Schindowski K., Kratzsch T., Peters J. et al. (2003) Impact of aging: sporadic, and genetic risk factors on vulnerability to apoptosis in Alzheimer's disease. Neuromolecular Med. 4, 161 178.
68. Schindowski K., Peters J., Gorriz C. et al. (2006) Apoptosis of CD4+ T and natural killer cells in Alzheimer's disease. Pharmacopsychiatry 39, 220 228.
69. Schindowski K., Eckert A., Peters J., Gorriz C., Schramm U., Weinandi T., Maurer K., Frolich L. Muller W. E. (2007) Increased T-cell reactivity and elevated levels of CD8+ memory T-cells in Alzheimer's disease-patients and T-cell hyporeactivity in an Alzheimer's disease-mouse model: implications for immunotherapy. Neuromolecular Med. 9, 340 354.
70. Schori H., Kipnis J., Yoles E., WoldeMussie E., Ruiz G., Wheeler L. A. Schwartz M. (2001) Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. Proc. Natl Acad. Sci. USA 98, 3398 3403.
71. Schwartz M. Moalem G. (2001) Beneficial immune activity after CNS injury: prospects for vaccination. J. Neuroimmunol. 113, 185 192.
72. Sedgwick J. D., Schwender S., Imrich H., Dorries R., Butcher G. W. ter Meulen V. (1991) Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc. Natl Acad. Sci. USA 88, 7438 7442.
73. Selkoe D. J. (1991) Alzheimer's disease. In the beginning. Nature 354, 432 433.
74. Selkoe D. J. (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav. Brain Res. 192, 106 113.
75. Shankar G. M., Li S., Mehta T. H. et al. (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 14, 837 842.
76. Shao H., Sun S. L., Kaplan H. J. Sun D. (2002) Induction of autoimmune encephalomyelitis and uveitis in B6 and (B6 × SJL) mice by peptides derived from myelin/oligodendrocyte glycoprotein. J. Neuroimmunol. 132, 117 122.
77. Shechter R., London A., Varol C. et al. (2008) Essential role for myeloid derived cells in the recovery from spinal cord injury. SfN abstract 758.22/E6.
78. Shechter R., London A., Varol C. et al. (2009) Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med. 6, e1000113.
79. Simard A. R. Rivest S. (2006) Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease. Mol. Psychiatry 11, 327 335.
80. Simard A. R., Soulet D., Gowing G., Julien J. P. Rivest S. (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49, 489 502.
81. Smith J. P., Lal V., Bowser D., Cappai R., Masters C. L. Ciccotosto G. D. (2009) Stimulus pattern dependence of the Alzheimer's disease amyloid-beta 42 peptide's inhibition of long term potentiation in mouse hippocampal slices. Brain Res. 1269, 176 184.
82. Snyder E. M., Nong Y., Almeida C. G. et al. (2005) Regulation of NMDA receptor trafficking by amyloid-beta. Nat. Neurosci. 8, 1051 1058.
83. Sonntag W. E., Lynch C., Thornton P., Khan A., Bennett S. Ingram R. (2000) The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. J. Anat. 197 (Pt 4), 575 585.
84. Sotthibundhu A., Sykes A. M., Fox B., Underwood C. K., Thangnipon W. Coulson E. J. (2008) Beta-amyloid(1-42) induces neuronal death through the p75 neurotrophin receptor. J. Neurosci. 28, 3941 3946.
85. Talmor M., Mirza A., Turley S., Mellman I., Hoffman L. A. Steinman R. M. (1998) Generation or large numbers of immature and mature dendritic cells from rat bone marrow cultures. Eur. J. Immunol. 28, 811 817.
86. Tesseur I., Zou K., Esposito L. et al. (2006) Deficiency in neuronal TGF-beta signaling promotes neurodegeneration and Alzheimer's pathology. J. Clin. Invest. 116, 3060 3069.
87. Tomidokoro Y., Harigaya Y., Matsubara E., Ikeda M., Kawarabayashi T., Okamoto K. Shoji M. (2000) Impaired neurotransmitter systems by Abeta amyloidosis in APPsw transgenic mice overexpressing amyloid beta protein precursor. Neurosci. Lett. 292, 155 158.
88. Town T. (2009) Alternative Abeta immunotherapy approaches for Alzheimer's disease. CNS Neurol. Disord. Drug Targets 8, 114 127.
89. Town T., Laouar Y., Pittenger C., Mori T., Szekely C. A., Tan J., Duman R. S. Flavell R. A. (2008) Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat. Med. 14, 681 687.
90. Tran M. H., Yamada K. Nabeshima T. (2002) Amyloid beta-peptide induces cholinergic dysfunction and cognitive deficits: a minireview. Peptides 23, 1271 1283.
91. Weiner H. L. Frenkel D. (2006) Immunology and immunotherapy of Alzheimer's disease. Nat. Rev. Immunol. 6, 404 416.
92. Wyss-Coray T. (2006a) Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med. 12, 1005 1015.
93. Wyss-Coray T. (2006b) Tgf-Beta pathway as a potential target in neurodegeneration and Alzheimer's. Curr. Alzheimer Res. 3, 191 195.
94. Wyss-Coray T. Mucke L. (2002) Inflammation in neurodegenerative disease-a double-edged sword. Neuron 35, 419 432.
95. Wyss-Coray T., Lin C., Yan F., Yu G. Q., Rohde M., McConlogue L., Masliah E. Mucke L. (2001) TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat. Med. 7, 612 618.
96. Yin K. J., Cirrito J. R., Yan P. et al. (2006) Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism. J. Neurosci. 26, 10939 10948.
97. Yoles E., Hauben E., Palgi O. et al. (2001) Protective autoimmunity is a physiological response to CNS trauma. J. Neurosci. 21, 3740 3748.
98. Zeng X. N., Sun X. L., Gao L., Fan Y., Ding J. H. Hu G. (2007) Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes. Mol. Cell. Neurosci. 34, 34 39.
99. Zhang W., Liang S., Wu J. Horuzsko A. (2008) Human inhibitory receptor immunoglobulin-like transcript 2 amplifies CD11b+Gr1+ myeloid-derived suppressor cells that promote long-term survival of allografts. Transplantation 86, 1125 1134.
100. Zhao W., Xie W., Xiao Q., Beers D. R. Appel S. H. (2006) Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron toxicity induced by activated microglia. J. Neurochem. 99, 1176 1187.
101. Zhao L., Lin S., Bales K. R. et al. (2009) Macrophage-mediated degradation of beta-amyloid via an apolipoprotein E isoform-dependent mechanism. J. Neurosci. 29, 3603 3612.
102. Zhong M. C., Kerlero de Rosbo N. Ben-Nun A. (2002) Multiantigen/ multiepitope-directed immune-specific suppression of "complex autoimmune encephalomyelitis" by a novel protein product of a synthetic gene. J. Clin. Invest. 110, 81 90.
103. Ziv Y., Avidan H., Pluchino S., Martino G. Schwartz M. (2006a) Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury. Proc. Natl Acad. Sci. USA 103, 13174 13179.
104. Ziv Y., Ron N., Butovsky O., Landa G., Sudai E., Greenberg N., Cohen H., Kipnis J. Schwartz M. (2006b) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat. Neurosci. 9, 268 275.
105. Zuo J., Neubauer D., Graham J., Krekoski C. A., Ferguson T. A. Muir D. (2002) Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. Exp. Neurol. 176, 221 228.