Immune processes in the pathogenesis of Parkinson’s disease – a potential role for microglia and nitric oxide
Anna Członkowska, Iwona Kurkowska-Jastrzębska, Andrzej Członkowski, Doris Peter, George B. Stefano
Med Sci Monit 2002; 8(8): RA165-177
It has been known for many years that immune system alterations occur in Parkinson’s disease (PD). Changes in lymphocyte populations in cerebrospinal fluid and blood, immunoglobulin synthesis, and cytokine and acute phase protein production have been observed in patients with PD. In this regard, PD patients exhibit a lower frequency of infections and cancer, suggesting that immune system stimulation may occur. This hypothesis is further supported by the observation of T-cell activation leading to the production of interferon γ in PD. As in other CNS degenerative diseases, in damaged regions in the brains of PD patients, there is evidence of inflammation, characterized by glial reaction (especially microglia), as well as increased expression of HLA-DR antigens, cytokines, and components of complement. These observations suggest that immune system mechanisms are involved in the pathogenesis of neuronal damage in PD. The cellular mechanisms of primary injury in PD have not been clarified, however,
but it is likely that mitochondrial mutations, oxidative stress and apoptosis play a role. Furthermore, inflammation initiated by neuronal damage in the striatum and the substantia nigra in PD may aggravate the course of the disease. These observations suggest that treatment
with anti-inflammatory drugs may act to slow progression of PD.
Keywords: Animals, Anti-Inflammatory Agents - therapeutic use, Apoptosis - physiology, Autoantibodies - metabolism, Brain - metabolism, Brain - pathology, Complement Activation - physiology, Cytokines - immunology, Cytokines - metabolism, Free Radicals - metabolism, Humans, Immune System - physiology, Microglia - physiology, Nitric Oxide - physiology, Parkinson Disease - drug therapy, Parkinson Disease - immunology, Parkinson Disease - pathology, T-Lymphocytes - cytology, T-Lymphocytes - immunology, T-Lymphocytes - metabolism