Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism.

Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Research Abstract Details 

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Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Abstract Text:

Tetyana Duka,Milan Rusnak,Robert E Drolet,Valeriy Duka,Christophe Wersinger,John L Goudreau,Anita Sidhu,

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.

Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Publishing Authors By Initials

T Duka,M Rusnak,RE Drolet,V Duka,C Wersinger,JL Goudreau,A Sidhu,

For similar microtubule-associated proteins: tau proteins research abstracts see: microtubule-associated proteins: tau proteins research

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Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The FASEB journal : official publication of the Fe

VOLUME: 20

Page Numbers: 2302-12

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 3

MONTH: Nov

YEAR: 2006

Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8804484

Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Keywords Mesh Terms:

KEYWORDS: tau Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. Information

Substance Name: tau Proteins

Registry Number: 0

Grant and Affiliation Information for Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism.

AFFILIATION: Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Washington, DC, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS-45326

ACRONYM: NS

MEDLINETA: FASEB J

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