Neuroinflammation is a fundamental process contributing to the death of neurons in Parkinson´s disease (PD). During this process, inflammatory microglia, which are the resident immune cells of the brain, secrete toxic substances leading to neuronal death. Therefore, understanding the mechanism that reverses the inflammatory activation of microglia is essential to protect from neurodegeneration. The objective of our project is to identify a dataset of molecules in microglia that play a role in the reversion from an inflammation to neuroprotection.
Since the transition of microglia from an inflammatory kind to a neuroprotective one can be followed structurally, we are planning to obtain this dataset through a screen. For this, we will modify the expression of the major regulators of inflammatory with small interfering RNAs (siRNA). Subsequently, we will treat the microglia with an anti-inflammatory agent that induces a cell shape change to a structure similar to healthy microglia. This change is associated with a decrease in the secretion of toxic substances and an increase in the expression of neuroprotective proteins. Thus, molecules whose modification inhibits the transition to a neuroprotective structure play a key role in this process and will be considered as potential drug targets.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The successful completion of our study will provide us with a dataset of drug targets that could lead to precise treatments to prevent neurodegeneration in PD.
We anticipate the identification of molecules implicated in the reversion from activated to neuroprotective microglia. This is the beginning for a comprehensive understanding of how microglia deactivation is regulated inside the cell, so that in the future this process could be controlled by a given drug treatment. Since this project is an unconventional and innovative approach to identify new drug targets, its outcome opens up a variety of novel investigation lines to PD treatment.