Pathogenicity of alpha-synuclein in various cell models for Parkinson’s disease

Quevedo Melo, T., 2018, [Groningen]: University of Groningen. 190 p.

Research output: ThesisThesis fully internal (DIV)Academic

Copy link to clipboard


  • Title and contents

    Final publisher's version, 234 KB, PDF-document

  • Chapter 1

    Final publisher's version, 682 KB, PDF-document

  • Chapter 2

    Final publisher's version, 891 KB, PDF-document

    Embargo ends: 18/04/2019

  • Chapter 3

    Final publisher's version, 2 MB, PDF-document

  • Chapter 4

    Final publisher's version, 3 MB, PDF-document

  • Chapter 5

    Final publisher's version, 8 MB, PDF-document

  • Chapter 6

    Final publisher's version, 1 MB, PDF-document

  • Chapter 7

    Final publisher's version, 161 KB, PDF-document

  • Chapter 8

    Final publisher's version, 131 KB, PDF-document

  • Acknowledgements

    Final publisher's version, 121 KB, PDF-document

  • Complete thesis

    Final publisher's version, 17 MB, PDF-document

    Embargo ends: 18/04/2019

  • Propositions

    Final publisher's version, 61 KB, PDF-document

  • Thaiany Quevedo Melo
Parkinson´s disease (PD) is considered the most common aging-related neurodegenerative disease in the world. Although a small percentage of PD is considered genetic, the major forms of PD are sporadic and considered the consequence of a yet unknown interaction between environmental conditions (e.g. pesticide exposure), lifestyle and genetic risk. The main characteristic of the disease is the presence of alpha-synuclein insoluble aggregates and (consequently?) the loss of dopaminergic neurons in the substantia nigra. The cellular mechanisms behind the death of dopaminergic neurons are still unknown. The PhD research by Thaiany Quevedo Melo addressed these mechanisms using different cell models mimicking PD-affected dopaminergic neurons. In the first model, cultured primary rat dopaminergic neurons were used and exposed to rotenone (a natural pesticide). The effects of rotenone on mitochondrial mobility, function and motor protein expression in the absence of alpha-synuclein aggregates were analyzed. Wild-type and mutant alpha-synuclein were expressed in the second cell model used, i.e. human differentiated dopaminergic neuron-like cells derived from SH-SY5Y cells. The protein aggregation, mitochondrial mobility, and treatment with the neuroprotective neuropeptide NAP were evaluated. In the third cell model, human dopaminergic neurons that were differentiated from iPS cells generated from patients with familial PD, the mitochondrial mobility and morphology were analyzed. Finally, the role of the motor protein Miro in the cellular stress caused by mutant alpha-synuclein was evaluated using yeast cell models. The studies in the different PD cell models revealed that alpha-synuclein impairs mitochondrial trafficking leading to Miro-dependent dysfunction of mitochondria and consequently cell death. Interestingly, the stabilization of microtubules using NAP appeared to recover mitochondrial trafficking and function. These findings strongly suggest that disrupted intracellular trafficking plays a crucial role in PD pathology and its recovery could be a potential therapeutical target.
Translated title of the contributionPathogeniteit van alfa-synucleïne in verschillende celmodellen voor de ziekte van Parkinson
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Award date18-Apr-2018
Place of Publication[Groningen]
Print ISBNs978-94-034-0556-8
Electronic ISBNs978-94-034-0557-5
Publication statusPublished - 2018

View graph of relations

Download statistics

No data available

ID: 56367189