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In-cell NMR monitoring of alpha-Synuclein aggregation in neuronal cells

Objective

Intracellular aggregation of the human amyloid protein alpha-synuclein is causally involved in Parkinson’s disease, a debilitating neurodegenerative disorder. The goal of this project is to combine low-resolution, fluorescence-imaging methods with high-resolution in-cell NMR and EPR spectroscopy techniques to derive macroscopic and microscopic insights into alpha-synuclein aggregate structures directly in neuronal cells.

To achieve this goal, we will employ different sets of cultured neurons and investigate intracellular alpha-synuclein aggregation under defined conditions of mitochondrial dysfunction and cellular oxidative stress, two of the most common denominators of the disease. Importantly, we will also establish a human stem cell model for studying alpha-synuclein aggregation with high-resolution in-cell NMR and EPR methods, by using induced pluripotent stem cell (iPSC) derived dopaminergic neurons from Parkinson’s disease patients and control individuals.

Results from this study will provide novel insights into the native mechanisms of intracellular aggregate formation and ultimately enable novel pharmacological approaches for therapeutic intervention.
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Host institution

WEIZMANN INSTITUTE OF SCIENCE

Address

Herzl Street 234
7610001 Rehovot

Israel

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 143 821,37

Beneficiaries (2)

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WEIZMANN INSTITUTE OF SCIENCE

Israel

EU Contribution

€ 1 143 821,37

FORSCHUNGSVERBUND BERLIN EV

Germany

EU Contribution

€ 852 678,63

Project information

Grant agreement ID: 647474

Status

Ongoing project

  • Start date

    1 November 2015

  • End date

    28 February 2021

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 996 500

  • EU contribution

    € 1 996 500

Hosted by:

WEIZMANN INSTITUTE OF SCIENCE

Israel