Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease

Recent data has indicated that the traditional view of Parkinson's disease (PD) as an isolated disorder of the nigrostriatal dopaminergic system alone is an oversimplification of its complex symptomatology. Aside from classical motor deficits, various non-motor symptoms including autonomic dysfunction, sensory and cognitive impairments as well as neuropsychiatric alterations and sleep disturbances are common in PD. Some of these non-motor symptoms can even antedate the motor problems. Many of them are associated with extranigral neuropathological changes, such as extensive α-synuclein pathology and also neuroinflammatory responses in specific brain regions, i.e. microglial activation, which has been implicated in several aspects of PD pathogenesis and progression. However, microglia do not represent a uniform population, but comprise a diverse group of cells with brain region-specific phenotypes that can exert beneficial or detrimental effects, depending on the local phenotype and context. Understanding how microglia can be neuroprotective in one brain region, while promoting neurotoxicity in another, will improve our understanding of the role of microglia in neurodegeneration in general, and of their role in PD pathology in particular. Since neuroinflammatory responses are in principle modifiable, such approaches could help to identify new targets or adjunctive therapies for the full spectrum of PD-related symptoms.

► Parkinson's disease (PD) is not limited to nigrostriatal degeneration alone.
► PD comprises several neurotransmitter systems and differential alpha-synuclein pathology as well.
► In addition to motor deficits, various non-motor symptoms are common in PD.
► Neuroinflammatory responses are involved in progression of PD.
► Region-specific microglial phenotypes may underlie the differential neuropathology and concomitant symptoms in PD.