Source:http://linkedlifedata.com/resource/pubmed/id/17077307
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
2006-11-1
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pubmed:abstractText |
Many neurodegenerative diseases associated with functional Tau dysregulation, including Alzheimer's disease (AD) and other tauopathies, also show alpha-synuclein (alpha-Syn) pathology, a protein associated with Parkinson's disease (PD) pathology. Here we show that treatment of primary mesencephalic neurons (48 h) or subchronic treatment of wild-type (WT) mice with the Parkinsonism-inducing neurotoxin MPP+/MPTP, results in selective dose-dependent hyperphosphorylation of Tau at Ser396/404 (PHF-1-reactive Tau, p-Tau), with no changes in pSer202 but with nonspecific increases in pSer262 levels. The presence of alpha-Syn was absolutely mandatory to observe MPP+/MPTP-induced increases in p-Tau levels, since no alterations in p-Tau were seen in transfected cells not expressing alpha-Syn or in alpha-Syn-/- mice. MPP+/MPTP also induced a significant accumulation of alpha-Syn in both mesencephalic neurons and in WT mice striatum. MPTP/MPP+ lead to differential alterations in p-Tau and alpha-Syn levels in a cytoskeleton-bound, vs. a soluble, cytoskeleton-free fraction, inducing their coimmunoprecipitation in the cytoskeleton-free fraction and neuronal soma. Subchronic MPTP exposure increased sarkosyl-insoluble p-Tau in striatum of WT but not alpha-Syn-/- mice. These studies describe a novel mechanism for MPTP neurotoxicity, namely a MPTP-inducible, strictly alpha-Syn-dependent, increased formation of PHF-1-reactive Tau, suggesting convergent overlapping pathways in the genesis of clinically divergent diseases such as AD and PD.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1530-6860
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2302-12
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17077307-Animals,
pubmed-meshheading:17077307-Cell Line,
pubmed-meshheading:17077307-Cloning, Molecular,
pubmed-meshheading:17077307-Disease Models, Animal,
pubmed-meshheading:17077307-Humans,
pubmed-meshheading:17077307-MPTP Poisoning,
pubmed-meshheading:17077307-Mice,
pubmed-meshheading:17077307-Mice, Inbred C57BL,
pubmed-meshheading:17077307-Mice, Knockout,
pubmed-meshheading:17077307-Phosphorylation,
pubmed-meshheading:17077307-Transfection,
pubmed-meshheading:17077307-alpha-Synuclein,
pubmed-meshheading:17077307-tau Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism.
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pubmed:affiliation |
Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Washington, DC, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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