Literature DB >> 12819014

Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies.

Deepak M Sampathu1, Benoit I Giasson, Aaron C Pawlyk, John Q Trojanowski, Virginia M-Y Lee.   

Abstract

alpha-Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are neurodegenerative disorders in which abnormal inclusions containing alpha-synuclein accumulate in selectively vulnerable neurons and glia. In this report, immunohistochemistry demonstrates ubiquitin in subsets of alpha-synuclein inclusions in dementia with Lewy bodies and multiple system atrophy. Biochemistry demonstrates that alpha-synuclein in the sodium dodecyl sulfate-soluble fractions of diseased brains is ubiquitinated, with mono- and di-ubiquitinated species predominating over polyubiquitinated forms. Similar immunohistochemical and biochemical characteristics were observed in an A53T mutant human alpha-synuclein transgenic mouse model of neurodegenerative alpha-synucleinopathies. Furthermore, in vitro ubiquitination of alpha-synuclein fibrils recapitulated the pattern of alpha-synuclein ubiquitination observed in human disease and the A53T alpha-synuclein mouse model. These results suggest that ubiquitination of alpha-synuclein is not required for inclusion formation and follows the fibrillization of alpha-synuclein.

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Year:  2003        PMID： 12819014      PMCID： PMC1868149          DOI： 10.1016/s0002-9440(10)63633-4

Source DB:  PubMed          Journal:  Am J Pathol        ISSN： 0002-9440            Impact factor:   4.307


  66 in total

1.  Proteasomal function is impaired in substantia nigra in Parkinson's disease.

Authors:  K S McNaught; P Jenner
Journal:  Neurosci Lett       Date:  2001-01-19       Impact factor: 3.046

Review 2.  The alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.

Authors:  M G Spillantini; M Goedert
Journal:  Ann N Y Acad Sci       Date:  2000       Impact factor: 5.691

3.  A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly.

Authors:  B I Giasson; I V Murray; J Q Trojanowski; V M Lee
Journal:  J Biol Chem       Date:  2000-11-01       Impact factor: 5.157

Review 4.  Alpha-synuclein and neurodegenerative diseases.

Authors:  M Goedert
Journal:  Nat Rev Neurosci       Date:  2001-07       Impact factor: 34.870

5.  Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity.

Authors:  Y Imai; M Soda; R Takahashi
Journal:  J Biol Chem       Date:  2000-11-17       Impact factor: 5.157

6.  An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene.

Authors:  S Hayashi; K Wakabayashi; A Ishikawa; H Nagai; M Saito; M Maruyama; T Takahashi; T Ozawa; S Tsuji; H Takahashi
Journal:  Mov Disord       Date:  2000-09       Impact factor: 10.338

7.  Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1.

Authors:  Y Zhang; J Gao; K K Chung; H Huang; V L Dawson; T M Dawson
Journal:  Proc Natl Acad Sci U S A       Date:  2000-11-21       Impact factor: 11.205

8.  Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies.

Authors:  J E Duda; B I Giasson; Q Chen; T L Gur; H I Hurtig; M B Stern; S M Gollomp; H Ischiropoulos; V M Lee; J Q Trojanowski
Journal:  Am J Pathol       Date:  2000-11       Impact factor: 4.307

9.  Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro.

Authors:  B I Giasson; K Uryu; J Q Trojanowski; V M Lee
Journal:  J Biol Chem       Date:  1999-03-19       Impact factor: 5.157

10.  Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease.

Authors:  K A Conway; J D Harper; P T Lansbury
Journal:  Nat Med       Date:  1998-11       Impact factor: 53.440
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  54 in total

Review 1.  Dynamic structural flexibility of α-synuclein.

Authors:  Danielle E Mor; Scott E Ugras; Malcolm J Daniels; Harry Ischiropoulos
Journal:  Neurobiol Dis       Date:  2015-12-31       Impact factor: 5.996

2.  Synthesis of a Bis-thio-acetone (BTA) Analogue of the Lysine Isopeptide Bond and its Application to Investigate the Effects of Ubiquitination and SUMOylation on α-Synuclein Aggregation and Toxicity.

Authors:  Yuka E Lewis; Tharindumala Abeywardana; Yu Hsuan Lin; Ana Galesic; Matthew R Pratt
Journal:  ACS Chem Biol       Date:  2016-01-12       Impact factor: 5.100

Review 3.  The North American Multiple System Atrophy Study Group.

Authors:  S Gilman; S J May; C W Shults; C M Tanner; W Kukull; V M-Y Lee; E Masliah; P Low; P Sandroni; J Q Trojanowski; L Ozelius; T Foroud
Journal:  J Neural Transm (Vienna)       Date:  2005-12       Impact factor: 3.575

Review 4.  New insight into neurodegeneration: the role of proteomics.

Authors:  Ramavati Pal; Guido Alves; Jan Petter Larsen; Simon Geir Møller
Journal:  Mol Neurobiol       Date:  2013-12-10       Impact factor: 5.590

5.  Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy.

Authors:  Nadia Stefanova; Markus Reindl; Manuela Neumann; Christian Haass; Werner Poewe; Philipp J Kahle; Gregor K Wenning
Journal:  Am J Pathol       Date:  2005-03       Impact factor: 4.307

6.  Synthetic polyubiquitinated α-Synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology.

Authors:  Mahmood Haj-Yahya; Bruno Fauvet; Yifat Herman-Bachinsky; Mirva Hejjaoui; Sudhir N Bavikar; Subramanian Vedhanarayanan Karthikeyan; Aaron Ciechanover; Hilal A Lashuel; Ashraf Brik
Journal:  Proc Natl Acad Sci U S A       Date:  2013-09-16       Impact factor: 11.205

7.  Aggregates assembled from overexpression of wild-type alpha-synuclein are not toxic to human neuronal cells.

Authors:  Li-Wen Ko; Hwai-Hwa C Ko; Wen-Lang Lin; Jayanranyan G Kulathingal; Shu-Hui C Yen
Journal:  J Neuropathol Exp Neurol       Date:  2008-11       Impact factor: 3.685

8.  Astrocyte-specific overexpression of Nrf2 delays motor pathology and synuclein aggregation throughout the CNS in the alpha-synuclein mutant (A53T) mouse model.

Authors:  Li Gan; Marcelo R Vargas; Delinda A Johnson; Jeffrey A Johnson
Journal:  J Neurosci       Date:  2012-12-05       Impact factor: 6.167

9.  Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein.

Authors:  Elisa A Waxman; Benoit I Giasson
Journal:  J Neuropathol Exp Neurol       Date:  2008-05       Impact factor: 3.685

10.  DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human alpha-syn toxicity.

Authors:  Chenere P Ramsey; Elpida Tsika; Harry Ischiropoulos; Benoit I Giasson
Journal:  Hum Mol Genet       Date:  2010-01-20       Impact factor: 6.150
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