Disease mechanisms as subtypes: Inflammation in Parkinson disease and related disorders

Neuroinflammation is a core feature of Parkinson disease (PD) and related disorders. Inflammation is detectable early in PD and persists throughout the disease state. Both the innate and the adaptive arms of the immune system are engaged in both human PD as well as in animal models of the disease. The upstream causes of PD are likely multiple and complex, which makes targeting of disease-modifying therapies based on etiological factors difficult. Inflammation is a broadly shared common mechanism and likely makes an important contribution to progression in most patients with manifest symptoms. Development of treatments targeting neuroinflammation in PD will require an understanding of the specific immune mechanisms which are active, their relative effects on both injury and neurorestoration, as well as the role of key variables likely to modulate the immune response: age, sex, the nature of the proteinopathies present, and the presence of copathologies. Studies characterizing the specific state of immune response in individuals and groups of people affected by PD will be essential to the development of targeted disease-modifying immunotherapies.