Immune processes in the pathogenesis of Parkinson's disease - a potential role for microglia and nitric oxide.
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 gamma 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.
Członkowska
Anna
A
2nd Department of Neurology, Institute of Psychiatry and Neurology, Department of Clinical and Experimental Pharmacology, Medical University, Warsaw, Poland.
Kurkowska-Jastrzebska
Iwona
I
Członkowski
Andrzej
A
Peter
Doris
D
Stefano
George B
GB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D001323:Autoantibodies / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003167:Complement Activation / Q000502:physiology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology; D017628:Microglia / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D016207:Cytokines; D005609:Free Radicals; D009569:Nitric Oxide