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N-ACETYLCYSTEINE AS A PARKINSON’S DISEASE THERAPY – CREATING A STRATEGY FOR DISEASE MODELING AND REPAIR
Abstract
Aims
Research in the last decade strongly suggests the use and development of neuroprotective/disease-modifying strategies as an absolute need for PD translational research. Under this concept of modality, is N-acetylcysteine (NAC), which has already demonstrated promising therapeutical effects in CNS applications. NAC, a natural compound with strong antioxidant effects, displays a pharmacological profile that implies potential benefits for PD, including neuroprotection and antiparkinsonian properties. Bearing this in mind, the aim of the present work was to explore the impact of NAC disease-modifying effects in a striatal 6-OHDA PD pre-clinical model of PD.
Methods
NAC (1200mg/kg) was given by oral gavage to 6-OHDA-induced striatal lesions. Dopaminergic neuronal survival/transmission, and motor performance were then accessed by histological and animal behaviour analysis.
Results
From the results, we have successfully established the striatal model of PD, producing a retrograde degeneration of the DA neurons. After treatment intervention, we observed that NAC potentiated the increase of TH-positive neurons and fibers both in the SNpc and striatum, thereby supporting the positive recovery observed in the motor performance outcomes. Similar observations were also found to DAT fluorescence intensity analysis, denoting that our strategy could also play a role on dopaminergic transmission.
Conclusions
Collectively, this work has provided an important proof-of-concept milestone regarding the therapeutical application of NAC. Nevertheless, based on the present results, understanding the complexity of NAC potentialities, and how its therapeutical properties interact with the cellular and molecular PD mechanisms may lead to a rational design of new therapeutic strategies for its functional modeling and repair.