The Protein Journal

, Volume 34, Issue 4, pp 291–303 | Cite as

Alpha-Synuclein Fibrils Interact with Dopamine Reducing its Cytotoxicity on PC12 Cells

  • Masoome Khalife
  • Dina Morshedi
  • Farhang Aliakbari
  • Amir Tayaranian Marvian
  • Hossein Mohammad Beigi
  • Sadegh Azimzadeh Jamalkandi
  • Francisco Pan-Montojo


Aggregated alpha-synuclein (α-SYN) is the major component of Lewy bodies and Lewy neurites, two of the pathological hallmarks of Parkinson’s disease (PD). Aggregation of α-SYN leads to toxic species involved in the degeneration of dopaminergic neurons in the midbrain. Different studies suggest a strong association between the presence of dopamine (DA) and the cell specific degeneration caused by α-SYN aggregates in PD. Despite extensive studies on the effect of DA on α-SYN fibrillation, it remains unclear how the simultaneous presence of DA and α-SYN influences the degeneration of dopaminergic neurons. In this study we show that separate treatments with specific doses of DA or early stage α-SYN aggregates (ESAA) are both cytotoxic to PC12 cells. Surprisingly, simultaneous treatment of cells with DA and ESAA significantly decreased this toxicity. This cytotoxicity was further reduced by the presence of heavier particles of α-SYN aggregates with more fibrillogenic characteristics. Spectrometric analysis revealed that α-SYN fibrils interact with DA even after the sample was dialyzed for 48 h, suggesting a strong interaction. Interestingly, digestion of unprotected N- and C-α-SYN-fibril terminals by proteinase K did not affect this interaction. Our results suggest that fibrillar forms of α-SYN with localized expanded active surfaces may interact with DA and moderate its cytotoxicity. Thus, highlighting the importance of fibrillar proteins in developing clinical approaches for amyloid diseases.


α-Synuclein Dopamine Fibrillation Fluorescent labeled α-synuclein, Neurodegeneration Parkinson’s disease Reactive oxygen species (ROS) 



Atomic Force Microscopy




Circular Dichroism




Dopamine quinone


Early Stages α-SYN Aggregates


Fourier Transform infrared


3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide


Optical Density


Parkinson’s Disease


Proteinase K


Propidium Iodide


Reactive Oxygen Species


Substantia Nigra pars compacta


Thioflavin T



This work was supported by the National Institute of Genetic Engineering and Biotechnology.

Compliance with Ethical Standards

Conflict of interest

The authors declare no potential conflict of interest.

Supplementary material

10930_2015_9625_MOESM1_ESM.pdf (214 kb)
Study of ASN fibrillation. Kinetic of the fibrillation monitored by (a) changes in ThT fluorescence intensity or (b) Congo red absorbance. The inset indicates maximum intensity of fluorescence. (c) Far-UV CD spectra of ASN obtained after 0-hours and 48-hours. (d) Fluorescence images of ASN fibrils dyed with ThT (PDF 214 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Masoome Khalife
    • 1
  • Dina Morshedi
    • 1
  • Farhang Aliakbari
    • 1
    • 2
  • Amir Tayaranian Marvian
    • 1
  • Hossein Mohammad Beigi
    • 1
    • 3
  • Sadegh Azimzadeh Jamalkandi
    • 1
    • 4
  • Francisco Pan-Montojo
    • 5
  1. 1.Department of Industrial and Environmental BiotechnologyNational Institute of Genetic Engineering and BiotechnologyTehranIran
  2. 2.Department of Medical BiotechnologySemnan University of Medical SciencesSemnanIran
  3. 3.Department of Chemical EngineeringTarbiat Modares UniversityTehranIran
  4. 4.Chemical Injuries Research CenterBaqiyatallah University of Medical SciencesTehranIran
  5. 5.Munich Cluster for Systems Neurology, SyNergy Clinician Scientist GroupKlinikum der Universität MünchenMunichGermany

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