Acta Neuropathologica

, Volume 115, Issue 4, pp 479–489

Curcumin inhibits aggregation of α-synuclein

  • Neeraj Pandey
  • Jeffrey Strider
  • William C. Nolan
  • Sherry X. Yan
  • James E. Galvin
Original Paper

Abstract

Aggregation of amyloid-beta protein (Aβ) is a key pathogenic event in Alzheimer’s disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Aβ amyloid and prevent further oligomerization of Aβ monomers onto growing amyloid β-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson’s disease (PD) and AD, we investigated the effect of curcumin on α-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1–6 μm. Greater than 32% decrease in mutant α-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.

Keywords

Alpha-synuclein Curcumin Parkinson’s disease Lewy bodies Amyloid Polyphenol 

Abbreviation

AS

alpha-Synuclein

PD

Parkinson’s disease

DLB

Dementia with Lewy bodies

AD

Alzheimer’s disease

Amyloid beta-protein

Supplementary material

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Supplemental Fig. 1 (JPEG 3.27 MB)
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Supplemental Fig. 2 (JPEG 2.89 MB)
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Supplemental Fig. 3 (JPEG 1.71 MB)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Neeraj Pandey
    • 1
  • Jeffrey Strider
    • 2
  • William C. Nolan
    • 3
  • Sherry X. Yan
    • 4
  • James E. Galvin
    • 4
    • 5
    • 6
  1. 1.Department of Anatomy and NeurobiologyWashington University School of MedicineSt LouisUSA
  2. 2.Department of NeuropathologyWashington University School of MedicineSt LouisUSA
  3. 3.Department of Biochemistry and Molecular BiologyWashington University School of MedicineSt LouisUSA
  4. 4.Department of NeurologyWashington University School of MedicineSt LouisUSA
  5. 5.Department of PsychiatryWashington University School of MedicineSt LouisUSA
  6. 6.Alzheimer Disease Research Center, Department of NeurobiologyWashington University School of MedicineSt LouisUSA

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