Journal of Molecular Neuroscience

, Volume 37, Issue 1, pp 25–36 | Cite as

Parkin Attenuates Wild-Type τ Modification in the Presence of β-Amyloid and α-Synuclein

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Abstract

Changes in tau (τ) metabolism comprise important pathological landmarks in the tauopathies with parkinsonism as well as Parkinson’s disease and Alzheimer’s disease. Mutations in the parkin gene are associated with Parkinson’s disease. Deposits of amyloid proteins, including Aβ and α-synuclein coexist in the brains of patients with dementia with Lewy bodies; however, it is not known how either of them interacts with τ to provoke neurofibrillary tangle formation across the tauopathies. Here, we show a role for parkin against τ pathology in the presence of intracellular Aβ or α-synuclein. Parkin attenuates four-repeat human τ, but not mutant P301L, hyperphosphorylation in the presence of intracellular Aβ1–42, or α-synuclein and decreases GSK-3β activity in amyloid-stressed M17 human neuroblastoma cells. These data suggest that parkin may counteract the alteration of τ metabolism in certain neurodegenerative diseases with τ cytopathy and parkinsonism.

Keywords

Parkin 4R human τ P301L Intracellular Aβ1–42 α-synuclein GSK-3β Phosphorylation Parkinsonism Dementia Tauopathies 

Abbreviations

PD

Parkinson’s disease

AD

Alzheimer’s disease

Aβ

β-amyloid

FTDP

Frontotemporal dementia

CBD

Corticobasal degeneration

PSP

Progressive supranuclear palsy

Syn

α-synuclein

Par

Parkin

τ

Tau

βAPP

β-amyloid precursor protein

MTT

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide

PHF

Paired helical filaments

NTF

Neurofibrillary tangle formation

4R τ

4-repeat tau

GSK-3β

Glycogen synthase kinase-3β

pGSK-3β

Phospho-GSK-3β

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Notes

Acknowledgments

This work was supported by a grant to Dr. Charbel. E-H Moussa from the American Parkinson’s Disease Association and NIH KO1 award AG030378 to Charbel E-H Moussa. This work was also supported in part by NIH grants NS04326 and AGO28108 to Dr. Anita Sidhu. The author would also like to thank Mr. Val Duka for his technical support.

Disclosure Statement

This work was supported by a grant to Charbel. E-H Moussa from the American Parkinson’s Disease Association and NIH-NIA K01 award AG030378 to Dr. Charbel E-H Moussa. This work was also supported in part by NIH grants NS04326 and AGO28108 to Dr. Anita Sidhu. As the sole author, I approve the submission of this work to Journal of Molecular Neuroscience and declare that this work has not and will not be submitted to any other journal while being reviewed by Journal of Molecular Neuroscience.

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© Humana Press 2008

Authors and Affiliations

  1. 1.Department of Biochemistry, Molecular and Cell BiologyGeorgetown University Medical CenterWashingtonUSA

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