An Inflammatory Pathomechanism for Parkinson's Disease?
Abstract:Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), striatal dopamine deficiency and appearance of Lewy bodies. Inflammatory and immune, or even autoimmune, stigmata, have been described in post-mortem brains of PD patients. Although disputed in humans, a reactive astrocytosis and a lymphocytic infiltration in the SNpc have been observed in animal models of PD, which need further examination. This review summarizes the current knowledge on brain inflammation in humans with PD, and how inflammation and/or (auto)immune reactions within the SNpc could be linked to other pathophysiological mechanisms that have been hypothesized for the etiology of PD, such as oxidative stress, exposure to neurotoxins, and postinfectious or post-traumatic injuries. In particular, we discuss how microglial cells could be activated during the course of PD, and present a new hypothesis that PD-linked protein (α-synuclein, in particular) aggregates could be implicated in their activation, to induce a chronic and sustained inflammation involved in the progression, at least, of the disease. The current status of anti-inflammatory agents, either already tried in PD clinical trials or putatively usefull as adjuvant therapies for PD, is also discussed.
Document Type: Research Article
Affiliations: Head, Lab. of Molecular Neurochemistry, Room W222, Georgetown University Medical Center, The Research Building, 3970 Reservoir Road, WASHINGTON, DC 20007, USA.
Publication date: 2006-03-01
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