Objective: The precise contribution of alpha-synuclein (ASYN) to neuronal dysfunction and death is still unclear. There is intense debate on the nature of the toxic species of ASYN, and little is still known about the molecular determinants of oligomerization and aggregation of ASYN in the cell. Thus, we are investigating the role of posttranslational modifications (PTMs) on aSyn biology and pathobiology.

Background: The aggregation of ASYN in Lewy bodies and Lewy neurites is the typical pathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. Furthermore, mutations in the gene encoding for ASYN are associated with familial and sporadic forms of PD, suggesting this protein plays a central role in the disease.

Method: By taking advantage of studies in model organisms, we are investigating the effect of various posttranslational modifications on the toxicity and aggregation of ASYN.

Results: We found that PTMs such as glycation and acetylation affect ASYN aggregation. In addition, we are also defining the molecular mechanisms triggered by extracellular forms of ASYN, a process associated with the spreading of pathology.

Conclusion: In total, our data shed light into the molecular underpinnings of synucleinopathies, opening novel perspectives for future therapeutic interventions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deciphering-the-role-of-posttranslational-modifications-on-%ce%b1-synuclein-aggregation-and-toxicity/