Impact of pharmacological treatment with Annexin A1 mimetic peptide in experimental model of Parkinson's Disease

Abstract

One of the focuses of our research group has been to investigate the pathophysiological relevance of the anti-inflammatory protein annexin A1 (AnxA1) and its mimetic peptides in different models of inflammation through a combination of histopathological, pharmacological, and ultrastructural analyses. On the other hand, we also seek to identify targets that mediate endogenous anti-inflammatory effects as new leads to innovative drug discoveries with therapeutic use and less adverse effects. Studies have been shown that AnxA1 is expressed in nervous tissue cells (neurons, astrocytes and microglia) and acts as a potent neuroprotective agent, regulating neuroinflammation. In addition, this protein can regulate the activation of the NLRP3 inflammasome, an important cytoplasmic sensor in inflammatory responses, whose expression is increased in neurodegenerative diseases such as Parkinson's disease (PD). However, the molecular mechanisms by which AnxA1 modulates cellular responses in PD are not yet determined. Thus, this project will evaluate the effect of pharmacological treatment with the AnxA1 mimetic peptide, Ac2-26, in an experimental model of PD. In addition, it will evaluate the effect of the lack of the endogenous protein AnxA1 on the development of PD in males and females using wild-type and AnxA1-knockout mice. Different methodologies will be used, such as: histological analysis (morphology, immunohistochemistry and immunofluorescence), molecular analysis (western blotting and RT-PCR), transcriptome, multiplex assays, that will contribute to a better understanding of the bioactivity of AnxA1 and its mimetic peptide in PD and its possible therapeutic application. Overall, this pioneering work will be able to elucidate the action of AnxA1 in PD taking into account the gender variable, which is important to seek more personalized treatments that directly impact the quality of life of patients. (AU)