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Anti-inflammatory Role of Activin-A in Protection against Alpha-synuclein-mediated Pathology

Objective/Rationale:             
Neuroinflammation is essential for the pathogenesis and progressionof Parkinson’s disease (PD); therefore, the identification of immunosuppressive agents that can control detrimental inflammation in the brain is critical for the treatment of the growing number of people with PD. Activin-A is a molecule that exerts strong neuroprotective functions. We plan to investigate the role of activin-A in synuclein-induced neuroinflammation and to examine whether activin-A can delay or halt synuclein toxic species transmission in the brain.

Project Description:
To explore the role of activin-A in PD pathogenesis, we will utilize two pre-clinical PD models and investigate the effects of activin-A following administration. In an opposite approach, we will inhibit the functions of activin-A. Using immunological and biochemical means, we will evaluate the potential role of activin-A as a therapeutic target in PD. The expression of activin-A in PD models and in affected tissues of PD patients will be studied.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
We anticipate that our results will uncover activin-A as a novel therapeutic target. Understanding its mechanisms may pave the way to new anti-inflammatory approaches to PD therapy.

Anticipated Outcome:          
We will evaluate activin-A as a regulator of neuroimmune responses and a critical controller of the progression of synuclein pathology in the brain. Importantly, our data may provide new insight in the development of substances manipulating activin-A, and/or its signalling pathways, that can pave the way to new therapeutic approaches for PD.


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