MECHANISMS OF PATHOGENESIS OF PARKINSON'S DISEASE

Abstract: 

Background: In Parkinson's Disease (PD), the second most common neurodegenerative disorder, the available symptomatic therapies gradually lose their efficacy and lead to significant complications.

There is need to develop a) neuroprotective therapies, and b) biomarkers for early diagnosis and follow-up. This need will be fulfilled through Elucidation of PD pathogenesis, which is the Aim of the current Proposal.

We have accordingly put together a multidisciplinary team, whose work is split in the following Work Packages:

  1. Multiple data suggest that alpha-synuclein (AS) is closely related to the pathogenesis of PD. It is unclear however whether AS represents a biomarker for PD. We have developed a sensitive ELISA for the measurement of AS in biological fluids, as well as a method to detect AS oligomers in Red Blood Cells. We will use such methods to assess AS in biological material from PD patients and controls and we will correlate the results with polymorphisms in the AS gene that may influence its transcriptional rate. We have also developed a unique neuronal cell model for the toxic effects of AS, which will be used to examine in a high-throughput fashion genes that influence such toxicity.
  2. We will examine in cellular and animal models the influence of secreted AS on microglial cells and its correlation with the neuroprotective factor Nurr1, which is genetically relevant to PD and exerts a putative anti-inflammatory action.
  3. We have found a genetic correlation between the gene hGDH2 and the age of onset of PD, thus linking the metabolism of glutamate with neurodegeneration. We propose to generate and characterize animal models based on these genetic data, and to develop pharmacological agents that inhibit GDH2.

Expected Results: We will decipher mechanisms linked to neurodegeneration in PD, and, in the process, help to develop novel biomarkers and therapeutic approaches.

Project info

Acronym:
PATHPD
Scientific Coordinator:
Stefanis Leonidas
Research Team 2 Leader:
Vassilatis Demitris
Research Team 3 Leader:
Plaitakis Andreas

Stats

I.D.:
398
Mis:
377206
Duration (months):
42
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4Λ39-0Ρ6

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