Microglia activation as a therapeutic target in multiple system atrophy: the timing, the good and the bad

Abstract

Microglial activation has turned out as one of the key factors during the disease process in neurodegenerative disorders. It has become clear that activated microglia contribute to the pathogenesis and progression of symptoms in a complex and multifaceted way, carrying out different functions which can affect the disease process in a positive or negative manner. We focus on neuroinflammation as a player in the pathogenesis of multiple system atrophy (MSA) – a rare neurodegenerative disorder characterized by α-synuclein accumulation in oligodendrocytes and selective neuronal loss. We discuss here recent findings in a transgenic mouse model of MSA supporting the notion of the bipolar effects of microglial activation linked to toxic pro-inflammatory signalling parallel to the neuroprotective α-synuclein clearance by microglia. Furthermore, we discuss microglial activation as a candidate therapeutic target for MSA and summarize preclinical data on the neuroprotective efficacy of myeloperoxidase inhibition dependent on the initiation of the treatment in relation to the clinical onset of the disease.