Original Paper

Acta Neuropathologica

, Volume 115, Issue 4, pp 479-489

First online:

Curcumin inhibits aggregation of α-synuclein

  • Neeraj PandeyAffiliated withDepartment of Anatomy and Neurobiology, Washington University School of Medicine
  • , Jeffrey StriderAffiliated withDepartment of Neuropathology, Washington University School of Medicine
  • , William C. NolanAffiliated withDepartment of Biochemistry and Molecular Biology, Washington University School of Medicine
  • , Sherry X. YanAffiliated withDepartment of Neurology, Washington University School of Medicine
  • , James E. GalvinAffiliated withDepartment of Neurology, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineAlzheimer Disease Research Center, Department of Neurobiology, Washington University School of Medicine Email author 

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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