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ACCEPTED MANUSCRIPT [261] G.K. Tofaris, M.G. Spillantini, Physiological and pathological properties of alpha-synuclein, Cell Mol Life Sci 64 (2007) 2194-2201. [262] K.F. Winklhofer, J. Tatzelt, The role of chaperones in Parkinson's disease and prion diseases, in: M. Gaestel (Ed.), Molecular chaperones in health and diseases, vol. 172, Springer-Verlag, 2006, pp. 221-258. [263] K. Beyer, Mechanistic aspects of Parkinson's disease: alpha-synuclein and the biomembrane, Cell Biochem Biophys 47 (2007) 285-299. [264] V.N. Uversky, Neuropathology, biochemistry, and biophysics of alpha- synuclein aggregation, Journal of neurochemistry 103 (2007) 17-37. [265] M.J. Volles, P.T. Lansbury, Jr., Zeroing in on the pathogenic form of alpha- synuclein and its mechanism of neurotoxicity in Parkinson's disease, Biochemistry 42 (2003) 7871-7878. [266] P.T. Lansbury, H.A. Lashuel, A century-old debate on protein aggregation and neurodegeneration enters the clinic, Nature 443 (2006) 774-779. [267] M.R. Cookson, M. van der Brug, Cell systems and the toxic mechanism(s) of alpha-synuclein, Experimental neurology Sep 29 [Epub ahead of print] (2007). [268] A.A. Cooper, A.D. Gitler, A. Cashikar, C.M. Haynes, K.J. Hill, B. Bhullar, K. ACCEPTED MANUSCRIPT Liu, K. Xu, K.E. Strathearn, F. Liu, S. Cao, K.A. Caldwell, G.A. Caldwell, G. Marsischky, R.D. Kolodner, J. Labaer, J.C. Rochet, N.M. Bonini, S. Lindquist, Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models, Science (New York, N.Y 313 (2006) 324-328. [269] W.W. Smith, H. Jiang, Z. Pei, Y. Tanaka, H. Morita, A. Sawa, V.L. Dawson, T.M. Dawson, C.A. Ross, Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity, Human molecular genetics 14 (2005) 3801-3811. 77
ACCEPTED MANUSCRIPT [270] A.M. Cuervo, L. Stefanis, R. Fredenburg, P.T. Lansbury, D. Sulzer, Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy, Science (New York, N.Y 305 (2004) 1292-1295. [271] E. Lindersson, R. Beedholm, P. Hojrup, T. Moos, W. Gai, K.B. Hendil, P.H. Jensen, Proteasomal inhibition by alpha-synuclein filaments and oligomers, The Journal of biological chemistry 279 (2004) 12924-12934. Epub 12004 Jan 12907. [272] L. Petrucelli, C. O'Farrell, P.J. Lockhart, M. Baptista, K. Kehoe, L. Vink, P. Choi, B. Wolozin, M. Farrer, J. Hardy, M.R. Cookson, Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons, Neuron 36 (2002) 1007-1019. [273] H. Snyder, K. Mensah, C. Theisler, J. Lee, A. Matouschek, B. Wolozin, Aggregated and monomeric alpha-synuclein bind to the S6' proteasomal protein and inhibit proteasomal function, The Journal of biological chemistry 278 (2003) 11753-11759. Epub 12003 Jan 11724. [274] L. Stefanis, K.E. Larsen, H.J. Rideout, D. Sulzer, L.A. Greene, Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces ACCEPTED MANUSCRIPT alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death, J Neurosci 21 (2001) 9549-9560. [275] Y. Tanaka, S. Engelender, S. Igarashi, R.K. Rao, T. Wanner, R.E. Tanzi, A. Sawa, D. V.L., T.M. Dawson, C.A. Ross, Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis, Human molecular genetics 10 (2001) 919- 926. [276] N. Gosavi, H.J. Lee, J.S. Lee, S. Patel, S.J. Lee, Golgi fragmentation occurs in 78
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Abstract ACCEPTED MANUSCRIPT Mitoch
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ACCEPTED MANUSCRIPT function mechan
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2.1.2. PINK1 substrates ACCEPTED MA
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