The reaction of α-synuclein with tyrosinase -: Possible implications for Parkinson disease

被引:118
|
作者
Tessari, Isabella [1 ]
Bisaglia, Marco [1 ]
Valle, Francesco [3 ]
Samori, Bruno [3 ]
Bergantino, Elisabetta [1 ]
Mammi, Stefano [2 ]
Bubacco, Luigi [1 ]
机构
[1] Univ Padua, Dept Biol, I-35121 Padua, Italy
[2] Univ Padua, Dept Chem Sci, I-35121 Padua, Italy
[3] Univ Bologna, Dept Biochem, I-40126 Bologna, Italy
关键词
D O I
10.1074/jbc.M709014200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative stress appears to be directly involved in the pathogenesis of Parkinson disease. Several different pathways have been identified for the production of oxidative stress conditions in nigral dopaminergic neurons, including a pathological accumulation of cytosolic dopamine with the subsequent production of toxic reactive oxygen species or the formation of highly reactive quinone species. On these premises, tyrosinase, a key copper enzyme known for its role in the synthesis of melanin in skin and hair, has been proposed to take part in the oxidative chemistry related to Parkinson disease. A study is herein presented of the in vitro reactivity of tyrosinase with alpha-synuclein, aimed at defining the molecular basis of their synergistic toxic effect. The results presented here indicate that, in conformity with the stringent specificity of tyrosinase, the exposed tyrosine sidechains are the reactive centers of alpha-synuclein. The reactivity of alpha-synuclein depends on whether it is free or membrane bound, and the chemical modifications on the tyrosinase-treated alpha-synuclein strongly influence its aggregation properties. On the basis of our results, we propose a cytotoxic model which includes a possible new toxic role for alpha-synuclein exacerbated by its direct chemical modification by tyrosinase.
引用
收藏
页码:16808 / 16817
页数:10
相关论文
共 50 条
  • [31] Upregulation of α-synuclein following immune activation: Possible trigger of Parkinson's disease
    Kasen, Alysa
    Houck, Christina
    Burmeister, Amanda R.
    Sha, Qiong
    Brundin, Lena
    Brundin, Patrik
    NEUROBIOLOGY OF DISEASE, 2022, 166
  • [32] α-Synuclein in Parkinson's Disease
    Stefanis, Leonidas
    COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2012, 2 (02):
  • [33] α-Synuclein and Parkinson's disease
    Burke, RE
    BRAIN RESEARCH BULLETIN, 1999, 50 (5-6) : 465 - 466
  • [34] α-synuclein and Parkinson's disease
    Iwatsubo, T
    SEIKAGAKU, 2002, 74 (06): : 477 - 482
  • [35] α-synuclein and Parkinson's Disease
    Recchia, A
    Debetto, P
    Negro, A
    Guidolin, D
    Skaper, SD
    Giusti, P
    FASEB JOURNAL, 2004, 18 (06): : 617 - 626
  • [36] α-synuclein and Parkinson's disease
    Golbe, LI
    PARKINSON'S DISEASE, 2003, 91 : 165 - 174
  • [37] α-Synuclein and Parkinson disease susceptibility
    Winkler, S.
    Hagenah, J.
    Lincoln, S.
    Heckman, M.
    Haugarvoll, K.
    Lohmann-Hedrich, K.
    Kostic, V.
    Farrer, M.
    Klein, C.
    NEUROLOGY, 2007, 69 (18) : 1745 - 1750
  • [38] β-Synuclein Intermediates α-Synuclein Neurotoxicity in Parkinson's Disease
    Xian, Meiyan
    Li, Jingwen
    Liu, Tingting
    Hou, Kaiying
    Sun, Lin
    Wei, Jianshe
    ACS CHEMICAL NEUROSCIENCE, 2024, 15 (13): : 2445 - 2453
  • [39] Advances in understanding the function of alpha-synuclein: implications for Parkinson's disease
    Calabresi, Paolo
    Di Lazzaro, Giulia
    Marino, Gioia
    Campanelli, Federica
    Ghiglieri, Veronica
    BRAIN, 2023, 146 (09) : 3587 - 3597
  • [40] Synergistic effects of pesticides and metals on the fibrillation of α-synuclein:: Implications for Parkinson's disease
    Uversky, VN
    Li, J
    Bower, K
    Fink, AL
    NEUROTOXICOLOGY, 2002, 23 (4-5) : 527 - 536