Rac1 at the crossroad of actin dynamics and neuroinflammation in Amyotrophic Lateral Sclerosis

Frontiers in Cellular Neuroscience

Volumn 8, Issue SEP, 2014, Pages

  D’Ambrosi, Nadia ^a   Rossi, Simona ^b,c   Gerbino, Valeria ^c,d   Cozzolino, Mauro ^b  

^a CATHOLIC UNIVERSITY   (Italy)

^b INSTITUTE OF TRANSLATIONAL PHARMACOLOGY   (Italy)

^c IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^d UNIVERSITY OF ROME TOR VERGATA   (Italy)

Author keywords

Amyotrophic Lateral Sclerosis (ALS); Microglia; Motor neurons; Neuroinflammation; NOX; Rac1; Reactive oxygen species; Spinal muscular atrophy (SMA)

Indexed keywords

BETA ACTIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; MESSENGER RNA; PROFILIN; PROTEIN; PROTEIN CDC42; PURINERGIC P2X7 RECEPTOR; RAC1 PROTEIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; SMALL INTERFERING RNA;

AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; CELL PROLIFERATION; CLINICAL TRIAL; ENZYME ACTIVITY; GENETIC ANALYSIS; HUMAN; IMMUNE RESPONSE; MICROGLIA; NERVOUS SYSTEM FUNCTION; NERVOUS SYSTEM INFLAMMATION; PATHOGENESIS; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SPINAL MUSCULAR ATROPHY;

EID: 84908215905     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00279     Document Type: Review

References (59)

1. Ackermann, B., Kröber, S., Torres-Benito, L., Borgmann, A., Peters, M., Hosseini Barkooie, S. M., et al. (2013). Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality. Hum. Mol. Genet. 22, 1328-1347. doi: 10.1093/hmg/dds540
2. Apolloni, S., Parisi, C., Pesaresi, M. G., Rossi, S., Carri, M. T., Cozzolino, M., et al. (2013). The NADPH oxidase pathway is dysregulated by the P2X7 receptor in the SOD1-G93 A microglia model of amyotrophic lateral sclerosis.J. Immunol. 190, 5187-5195. doi: 10.4049/jimmunol.1203262
3. Appel, S. H., Zhao, W., Beers, D. R., and Henkel, J. S. (2011). The microglial-motoneuron dialogue in ALS. Acta Myol. 30, 4-8.
4. Bedard, K., and Krause, K. H. (2007). The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol. Rev. 87, 245-313. doi: 10.1152/physrev.00044.2005
5. Birbach, A. (2008). Profilin, a multi-modal regulator of neuronal plasticity. Bioessays 30, 994-1002. doi: 10.1002/bies.20822
6. Boillée, S., Vande Velde, C., and Cleveland, D. W. (2006). ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 52, 39-59. doi: 10.1016/j.neuron.2006.09.018
7. Bowerman, M., Beauvais, A., Anderson, C. L., and Kothary, R. (2010). Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model. Hum. Mol. Genet. 19, 1468-1478. doi: 10.1093/hmg/ddq021
8. Bowerman, M., Murray, L. M., Boyer, J. G., Anderson, C. L., and Kothary, R. (2012). Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy. BMC Med. 10:24. doi: 10.1186/1741-7015-10-24
9. Burghes, A. H., and Beattie, C. E. (2009). Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat. Rev. Neurosci. 10, 597-609. doi: 10.1038/nrn2670
10. Cooper-Knock, J., Shaw, P. J., and Kirby, J. (2014). The widening spectrum of C9ORF72-related disease; genotype/phenotype correlations and potential modifiers of clinical phenotype. Acta Neuropathol. 127, 333-345. doi: 10.1007/s00401-014-1251-9
11. Cozzolino, M., Pesaresi, M. G., Gerbino, V., Grosskreutz, J., and Carri, M. T. (2012). Amyotrophic lateral sclerosis: new insights into underlying molecular mechanisms and opportunities for therapeutic intervention. Antioxid. Redox Signal. 17, 1277-1330. doi: 10.1089/ars.2011.4328
12. DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., et al. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245-256. doi: 10.1016/j.neuron.2011.09.011
13. Fischer, L. R., Culver, D. G., Tennant, P., Davis, A. A., Wang, M., Castellano-Sanchez, A., et al. (2004). Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp. Neurol. 185, 232-240. doi: 10.1016/j.expneurol.2003.10.004
14. Gerbino, V., Carri, M. T., Cozzolino, M., and Achsel, T. (2013). Mislocalised FUS mutants stall spliceosomal snRNPs in the cytoplasm. Neurobiol. Dis. 55, 120-128. doi: 10.1016/j.nbd.2013.03.003
15. Groen, E. J., Fumoto, K., Blokhuis, A. M., Engelen-Lee, J., Zhou, Y., van den Heuvel, D. M., et al. (2013). ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN. Hum. Mol. Genet. 22, 3690-3704. doi: 10.1093/hmg/ddt222
16. Harraz, M. M., Marden, J. J., Zhou, W., Zhang, Y., Williams, A., Sharov, V. S., et al. (2008). SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J. Clin. Invest. 118, 659-670. doi: 10.1172/JCI34060
17. Henkel, J. S., Beers, D. R., Zhao, W., and Appel, S. H. (2009). Microglia in ALS: the good, the bad and the resting. J. Neuroimmune Pharmacol. 4, 389-398. doi: 10.1007/s11481-009-9171-5
18. Iguchi, Y., Katsuno, M., Niwa, J., Yamada, S., Sone, J., Waza, M., et al. (2009). TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases. J. Biol. Chem. 284, 22059-22066. doi: 10.1074/jbc.M109.012195
19. Jacquier, A., Buhler, E., Schafer, M. K., Bohl, D., Blanchard, S., Beclin, C., et al. (2006). Alsin/Rac1 signaling controls survival and growth of spinal motoneurons. Ann. Neurol. 60, 105-117. doi: 10.1002/ana.20886
20. Jung, H., Gkogkas, C. G., Sonenberg, N., and Holt, C. E. (2014). Remote control of gene function by local translation.Cell 157, 26-40. doi: 10.1016/j.cell.2014.03.005
21. Jung, H., Yoon, B. C., and Holt, C. E. (2012). Axonal mRNA localization and local protein synthesis in nervous system assembly, maintenance and repair. Nat. Rev. Neurosci. 13, 308-324. doi: 10.1038/nrn3210
22. Kanekura, K., Hashimoto, Y., Kita, Y., Sasabe, J., Aiso, S., Nishimoto, I., et al. (2005). A Rac1/phosphatidylinositol 3-kinase/Akt3 anti-apoptotic pathway, triggered by AlsinLF, the product of the ALS2 gene, antagonizes Cu/Zn-superoxide dismutase (SOD1) mutant-induced motoneuronal cell death. J. Biol. Chem. 280, 4532-4543. doi: 10.1074/jbc.m410508200
23. Kariya, S., Park, G. H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M. S., et al. (2008). Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum. Mol. Genet. 17, 2552-2569. doi: 10.1093/hmg/ddn156
24. Li, Q., Spencer, N. Y., Pantazis, N. J., and Engelhardt, J. F. (2011). Alsin and SOD1(G93A) proteins regulate endosomal reactive oxygen species production by glial cells and proinflammatory pathways responsible for neurotoxicity. J. Biol. Chem. 286, 40151-40162. doi: 10.1074/jbc.M111.279711
25. Liao, B., Zhao, W., Beers, D. R., Henkel, J. S., and Appel, S. H. (2012). Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp. Neurol. 237, 147-152. doi: 10.1016/j.expneurol.2012.06.011
26. Ling, S. C., Polymenidou, M., and Cleveland, D. W. (2013). Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 79, 416-438. doi: 10.1016/j.neuron.2013.07.033
27. Linseman, D. A., and Loucks, F. A. (2008). Diverse roles of Rho family GTPases in neuronal development, survival and death. Front. Biosci. 13, 657-676. doi: 10.2741/2710
28. Lorenzetto, E., Ettorre, M., Pontelli, V., Bolomini-Vittori, M., Bolognin, S., Zorzan, S., et al. (2013). Rac1 selective activation improves retina ganglion cell survival and regeneration. PLoS One 8:e64350. doi: 10.1371/journal.pone.0064350
29. Majumder, P., Chen, Y. T., Bose, J. K., Wu, C. C., Cheng, W. C., Cheng, S. J., et al. (2012). TDP-43 regulates the mammalian spinogenesis through translational repression of Rac1. Acta Neuropathol. 124, 231-245. doi: 10.1007/s00401-012-1006-4
30. Marchetto, M. C., Muotri, A. R., Mu, Y., Smith, A. M., Cezar, G. G., and Gage, F. H. (2008). Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell3, 649-657. doi: 10.1016/j.stem.2008.10.001
31. Marden, J. J., Harraz, M. M., Williams, A. J., Nelson, K., Luo, M., Paulson, H., et al. (2007). Redox modifier genes in amyotrophic lateral sclerosis in mice. J. Clin. Invest. 117, 2913-2919. doi: 10.1172/jci31265
32. Mitchell, L., Hobbs, G. A., Aghajanian, A., and Campbell, S. L. (2013). Redox regulation of Ras and Rho GTPases: mechanism and function. Antioxid. Redox Signal. 18, 250-258. doi: 10.1089/ars.2012.4687
33. Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., et al. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133. doi: 10.1126/science.1134108
34. Nölle, A., Zeug, A., Van Bergeijk, J., Tönges, L., Gerhard, R., Brinkmann, H., et al. (2011). The spinal muscular atrophy disease protein SMN is linked to the Rho-kinase pathway via profilin. Hum. Mol. Genet. 20, 4865-4878. doi: 10.1093/hmg/ddr425
35. Oprea, G. E., Krober, S., McWhorter, M. L., Rossoll, W., Muller, S., Krawczak, M., et al. (2008). Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science 320, 524-527. doi: 10.1126/science.1155085
36. Panzeri, C., De Palma, C., Martinuzzi, A., Daga, A., De Polo, G., Bresolin, N., et al. (2006). The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain 129, 1710-1719. doi: 10.1093/brain/awl104
37. Pesaresi, M. G., Amori, I., Giorgi, C., Ferri, A., Fiorenzo, P., Gabanella, F., et al. (2011). Mitochondrial redox signalling by p66Shc mediates ALS-like disease through Rac1 inactivation. Hum. Mol. Genet. 20, 4196-4208. doi: 10.1093/hmg/ddr347
38. Philips, T., and Robberecht, W. (2011). Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10, 253-263. doi: 10.1016/s1474-4422(11)70015-1
39. Pollari, E., Goldsteins, G., Bart, G., Koistinaho, J., and Giniatullin, R. (2014). The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis. Front. Cell. Neurosci. 8:131. doi: 10.3389/fncel.2014.00131
40. Rage, F., Boulisfane, N., Rihan, K., Neel, H., Gostan, T., Bertrand, E., et al. (2013). Genome-wide identification of mRNAs associated with the protein SMN whose depletion decreases their axonal localization. RNA 19, 1755-1766. doi: 10.1261/rna.040204.113
41. Renton, A. E., Chio, A., and Traynor, B. J. (2014). State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 17, 17-23. doi: 10.1038/nn.3584
42. Renton, A. E., Majounie, E., Waite, A., Simon-Sanchez, J., Rollinson, S., Gibbs, J. R., et al. (2011). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257-268. doi: 10.1016/j.neuron.2011.09.010
43. Rizzo, F., Riboldi, G., Salani, S., Nizzardo, M., Simone, C., Corti, S., et al. (2014). Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell. Mol. Life Sci. 71, 999-1015. doi: 10.1007/s00018-013-1480-4
44. Rossoll, W., Jablonka, S., Andreassi, C., Kroning, A. K., Karle, K., Monani, U. R., et al. (2003). Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J. Cell Biol. 163, 801-812. doi: 10.1083/jcb.200304128
45. Schrank, B., Gotz, R., Gunnersen, J. M., Ure, J. M., Toyka, K. V., Smith, A. G., et al. (1997). Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc. Natl. Acad. Sci. U S A 94, 9920-9925. doi: 10.1073/pnas.94.18.9920
46. Sorce, S., and Krause, K. H. (2009). NOX enzymes in the central nervous system: from signaling to disease.Antioxid. Redox Signal. 11, 2481-2504. doi: 10.1089/ARS.2009.2578
47. Takata, M., Tanaka, H., Kimura, M., Nagahara, Y., Tanaka, K., Kawasaki, K., et al. (2013). Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis. Br. J. Pharmacol. 170, 341-351. doi: 10.1111/bph.12277
48. Tönges, L., Günther, R., Suhr, M., Jansen, J., Balck, A., Saal, K. A., et al. (2014). Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis. Glia 62, 217-232. doi: 10.1002/glia.22601
49. Topp, J. D., Gray, N. W., Gerard, R. D., and Horazdovsky, B. F. (2004). Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. J. Biol. Chem. 279, 24612-24623. doi: 10.1074/jbc.m313504200
50. Travaglione, S., Loizzo, S., Ballan, G., Fiorentini, C., and Fabbri, A. (2014). The E. coli CNF1 as a pioneering therapy for the central nervous system diseases. Toxins (Basel) 6, 270-282. doi: 10.3390/toxins6010270
51. Trumbull, K. A., McAllister, D., Gandelman, M. M., Fung, W. Y., Lew, T., Brennan, L., et al. (2012). Diapocynin and apocynin administration fails to significantly extend survival in G93A SOD1 ALS mice. Neurobiol. Dis. 45, 137-144. doi: 10.1016/j.nbd.2011.07.015
52. Turner, B. J., Alfazema, N., Sheean, R. K., Sleigh, J. N., Davies, K. E., Horne, M. K., et al. (2014). Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.Neurobiol. Aging 35, 906-915. doi: 10.1016/j.neurobiolaging.2013.09.030
53. van Bergeijk, J., Rydel-Konecke, K., Grothe, C., and Claus, P. (2007). The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus. FASEB J. 21, 1492-1502. doi: 10.1096/fj.06-7136com
54. van Blitterswijk, M., Baker, M. C., Bieniek, K. F., Knopman, D. S., Josephs, K. A., Boeve, B., et al. (2013). Profilin-1 mutations are rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia. Amyotroph. Lateral Scler. Frontotemporal Degener. 14, 463-469. doi: 10.3109/21678421.2013.787630
55. Vance, C., Rogelj, B., Hortobagyi, T., De Vos, K. J., Nishimura, A. L., Sreedharan, J., 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
56. Wu, C. H., Fallini, C., Ticozzi, N., Keagle, P. J., Sapp, P. C., Piotrowska, K., et al. (2012). Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488, 499-503. doi: 10.1038/nature1128
57. Wu, D. C., Re, D. B., Nagai, M., Ischiropoulos, H., and Przedborski, S. (2006). The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc. Natl. Acad. Sci. U S A103, 12132-12137. doi: 10.1073/pnas.0603670103
58. Yamazaki, T., Chen, S., Yu, Y., Yan, B., Haertlein, T. C., Carrasco, M. A., et al. (2012). FUS-SMN protein interactions link the motor neuron diseases ALS and SMA. Cell Rep. 2, 799-806. doi: 10.1016/j.celrep.2012.08.025
59. Yang, Y., Hentati, A., Deng, H. X., Dabbagh, O., Sasaki, T., Hirano, M., et al. (2001). The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat. Genet. 29, 160-165. doi: 10.1038/ng1001-160