Galectin-3 Deletion Reduces LPS and Acute Colitis-Induced Pro-Inflammatory Microglial Activation in the Ventral Mesencephalon.

Parkinson's disease is a highly prevalent neurological disorder for which there is currently no cure. Therefore, the knowledge of risk factors as well as the development of new putative molecular targets is mandatory. In this sense, peripheral inflammation, especially the originated in the colon, is emerging as a predisposing factor for suffering this disease. We have largely studied the pleiotropic roles of galectin-3 in driving microglia-associated immune responses. However, studies aimed at elucidating the role of galectin-3 in peripheral inflammation in terms of microglia polarization are lacking. To achieve this, we have evaluated the effect of galectin-3 deletion in two different models of acute peripheral inflammation: intraperitoneal injection of lipopolysaccharide or gut inflammation induced by oral administration of dextran sodium sulfate. We found that under peripheral inflammation the number of microglial cells and the expression levels of pro-inflammatory mediators take place specifically in the dopaminergic system, thus supporting causative links between Parkinson's disease and peripheral inflammation. Absence of galectin-3 highly reduced neuroinflammation in both models, suggesting an important central regulatory role of galectin-3 in driving microglial activation provoked by the peripheral inflammation. Thus, modulation of galectin-3 function emerges as a promising strategy to minimize undesired microglia polarization states.

Brainiac Caspases: Beyond the Wall of Apoptosis.

For the last two decades, caspases, a family of cysteine-aspartic proteases, have evolved from being considered solely as regulators of apoptosis or inflammation to having a wider range of functions. In this mini review, we focus on the most recent "non-apoptotic" roles of caspases in the CNS, particularly in neurons, astrocytes and oligodendrocytes. Non-apoptotic caspase functions in microglia have already been reviewed extensively elsewhere. Here we discuss the involvement of caspases in the activation of the inflammasome, autophagy, and non-apoptotic forms of cell death such as necroptosis and pyroptosis. Also, we review the involvement of caspases in synapses and the processing of aggregates key to neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's diseases. Likewise, we mention the recently described involvement of caspases in mitochondrial biogenesis, which is a function independent of the enzymatic activity. We conclude discussing the relevance that "new" functions of caspases have in the CNS and the future of this field of research.