Hostname: page-component-848d4c4894-nmvwc Total loading time: 0 Render date: 2024-06-22T13:11:19.912Z Has data issue: false hasContentIssue false
  • English
  • Français

Fas expression promotes proteasomal activity in toxin-induced parkinsonism

Published online by Cambridge University Press:  24 June 2014

Anne M. Landau ,
Rosmarie Siegrist-Johnstone  and
Julie Desbarats
Anne M. Landau*
Affiliation:
Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada Department of Nuclear Medicine, PET Center and Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark
Rosmarie Siegrist-Johnstone
Affiliation:
Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
Julie Desbarats
Affiliation:
Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
*
Anne M. Landau, Department of Nuclear Medicine, PET Center and Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Norrebrogade 44, Building 10G, 8000 Aarhus C, Denmark. Tel: +45 8949 4378; Fax: +45 8949 3020; E-mail: annie@pet.auh.dk
Get access Rights & Permissions [Opens in a new window]

Extract

Objective: Fas (CD95), commonly categorised as a death receptor due to its well-defined role in apoptosis, can paradoxically also promote neuroprotection. We have previously found that defects in Fas signalling render mice highly susceptible to neural degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease (PD). Decreased activity of the ubiquitin proteasome system and accumulation of protein aggregates are implicated in PD pathogenesis. Here, we investigate the relationship between Fas and ubiquitin proteasomal activity in neuronal cells.

Methods: We performed proteasome assays in neuroblastoma cells and in midbrain cultures of wild-type and Fas-deficient mice.

Results: Neuroblastoma cells upregulated proteasomal activity in response to an activating Fas antibody in vitro. Furthermore, neural tissue from Fas-deficient mice showed decreased proteasomal activity compared with the tissue from wild-type mice when exposed to a PD-inducing toxin in vivo.

Conclusion: These findings suggest that mechanisms for Fas-mediated neuroprotection may include Fas-induced upregulation of proteasomal activity, and consequently less accumulation of toxic protein aggregates.

Keywords

CD951-methyl-4-phenyl-1,2,3,6-tetrahydropyridineParkinson's diseaseubiquitin
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 3 , June 2012 , pp. 166 - 171
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Nagata, S.Apoptosis by death factor. Cell 1997;88:355–365.CrossRefGoogle ScholarPubMed
2.Martin-Villalba, A, Herr, I, Jeremias, I et al. CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. J Neurosci 1999;19:3809–3817.CrossRefGoogle ScholarPubMed
3.Raoul, C, Estevez, AG, Nishimune, H et al. Motoneuron death triggered by a specific pathway downstream of Fas. Potentiation by ALS-linked SOD1 mutations. Neuron 2002;35:1067–1083.CrossRefGoogle ScholarPubMed
4.Raoul, C, Henderson, CE, Pettmann, B.Programmed cell death of embryonic motoneurons triggered through the Fas death receptor. J Cell Biol 1999;147:1049–1062.CrossRefGoogle ScholarPubMed
5.Peter, ME, Budd, RC, Desbarats, J et al. The CD95 receptor: apoptosis revisited. Cell 2007;129:447–450.CrossRefGoogle ScholarPubMed
6.Choi, C, Benveniste, EN.Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses. Brain Res Brain Res Rev 2004;44:65–81.CrossRefGoogle ScholarPubMed
7.Desbarats, J, Birge, RB, Mimouni-Rongy, M, Weinstein, DE, Palerme, JS, Newell, MK.Fas engagement induces neurite growth through ERK activation and p35 upregulation. Nat Cell Biol 2003;5:118–125.CrossRefGoogle ScholarPubMed
8.Landau, AM, Luk, KC, Jones, ML et al. Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease. J Exp Med 2005;202:575–581.CrossRefGoogle Scholar
9.Ciechanover, A, Brundin, P.The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron 2003;40:427–446.CrossRefGoogle ScholarPubMed
10.McNaught, KS, Jackson, T, JnoBaptiste, R, Kapustin, A, Olanow, CW.Proteasomal dysfunction in sporadic Parkinson's disease. Neurology 2006;66(10 Suppl. 4):S37–S49.CrossRefGoogle ScholarPubMed
11.Shimura, H, Schlossmacher, MG, Hattori, N et al. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science 2001 293:263–269.CrossRefGoogle ScholarPubMed
12.Leroy, E, Boyer, R, Auburger, G et al. The ubiquitin pathway in Parkinson's disease. Nature 1998;395:451–452.CrossRefGoogle ScholarPubMed
13.McNaught, KS, Belizaire, R, Isacson, O, Jenner, P, Olanow, CW.Altered proteasomal function in sporadic Parkinson's disease. Exp Neurol 2003;179:38–46.CrossRefGoogle ScholarPubMed
14.McNaught, KS, Belizaire, R, Jenner, P, Olanow, CW, Isacson, O.Selective loss of 20S proteasome alpha-subunits in the substantia nigra pars compacta in Parkinson's disease. Neurosci Lett 2002;326:155–158.CrossRefGoogle ScholarPubMed
15.McNaught, KS, Jnobaptiste, R, Jackson, T, Jengelley, TA.The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease. Synapse 2010;64:241–250.CrossRefGoogle ScholarPubMed
16.McNaught, KS, Perl, DP, Brownell, AL, Olanow, CW.Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann Neurol 2004;56:149–162.CrossRefGoogle ScholarPubMed
17.Fornai, F, Lenzi, P, Gesi, M et al. Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition. J Neurosci 2003;23:8955–8966.CrossRefGoogle ScholarPubMed
18.Sun, F, Anantharam, V, Zhang, D, Latchoumycandane, C, Kanthasamy, A, Kanthasamy, AG.Proteasome inhibitor MG-132 induces dopaminergic degeneration in cell culture and animal models. Neurotoxicology 2006;27:807–815.CrossRefGoogle ScholarPubMed
19.Fujita, M, Sugama, S, Nakai, M et al. alpha-synuclein stimulates differentiation of osteosarcoma cells: Relevance to downregulation of proteasome activity. J Biol Chem 2007;282:5736–5748.Google ScholarPubMed
20.Chu, Y, Dodiya, H, Aebischer, P, Olanow, CW, Kordower, JH.Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions. Neurobiol Dis 2009;35:385–398.CrossRefGoogle ScholarPubMed
21.Smeyne, M, Smeyne, RJ.Method for culturing postnatal substantia nigra as an in vitro model of experimental Parkinson's disease. Brain Res Brain Res Protoc 2002;9:105–111.CrossRefGoogle Scholar
22.Song, EJ, Yim, SH, Kim, E, Kim, NS, Lee, KJ.Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway. Mol Cell Biol 2005;25:2511–2524.CrossRefGoogle ScholarPubMed
23.Ferrer, I, Blanco, R, Cutillas, B, Ambrosio, S.Fas and Fas-L expression in Huntington's disease and Parkinson's disease. Neuropathol Appl Neurobiol 2000;26:424–433.CrossRefGoogle ScholarPubMed
24.Mogi, M, Harada, M, Kondo, T et al. The soluble form of Fas molecule is elevated in parkinsonian brain tissues. Neurosci Lett 1996;220:195–198.CrossRefGoogle ScholarPubMed