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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.

Call for proposal

ERC-2014-CoG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

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)

WEIZMANN INSTITUTE OF SCIENCE
Israel
EU contribution
€ 1 143 821,37
Address
Herzl Street 234
7610001 Rehovot
Activity type
Higher or Secondary Education Establishments
FORSCHUNGSVERBUND BERLIN EV

Participation ended

Germany
EU contribution
€ 852 678,63
Address
Rudower Chaussee 17
12489 Berlin
Activity type
Research Organisations