The influence of microglia on the pathogenesis of Parkinson's disease
Section snippets
Parkinson's disease
Parkinson's disease (PD) was first described in 1817 by Dr. James Parkinson, a London physician, in ‘An Essay on the Shaking Palsy’ (Parkinson, 1817). It is the second most common neurodegenerative disorder, after Alzheimer's disease (AD). The incidence of PD is age-related; in developed countries, it affects approximately 1% of the population aged over 60 years (Nussbaum and Ellis, 2003) and increases sharply with age after 60 years, rising to over 4% in the oldest populations (de Lau and
Microglia
Microglia are the resident immune-competent cells of the CNS and have a role in monitoring the brain for immune insults and invading pathogens. Ramón and Cajal considered microglia to be part of the ‘third element’ of the CNS, being neither neuronal nor astrocytic (Cajal, 1913). In the 1930s, Pio del Rio Hortega, a student of Cajal, estimated that they make up approximately 12% of the cells in the brain (del Rio Hortega, 1932). Microglia have a mesohaemopoietic origin and are likely to arise
Inflammation in Parkinson's disease patients
The first evidence for a role for inflammation in PD came from a post-mortem study – in 1998, McGeer and colleagues found activated microglia and T-lymphocytes in the SNpc of a PD patient. Since then, there have been numerous studies which support a role for neuroinflammatory processes in PD (Hirsch and Hunot, 2009, McGeer and McGeer, 2004, Orr et al., 2002, Tansey et al., 2007). In addition to the presence of activated microglia and pro-inflammatory cytokines (both of which are discussed
Anti-inflammatory therapies
As the evidence accumulates for a detrimental role of inflammation in the pathogenesis of PD, a host of anti-inflammatory agents are now under investigation (Table 1). Indeed data generated from use of non-steroidal anti-inflammatory drugs, microglial inhibitors and anti-inflammatory cytokines in animal and cellular studies, have supported the notion that control of neuroinflammation is a strategy worth pursuing in the effort to retard or even prevent degeneration of dopaminergic neurons in PD.
Conclusion
The death of dopaminergic neurons in the SNpc is the key pathology of PD. Therefore, it is imperative that research is undertaken, not only in areas which could provide protective strategies for the remaining neurons, or which involve dopaminergic neuronal cell replacement therapies, but also into understanding the fundamental mechanisms by which these cells die. Although the precise role of inflammation in the pathogenesis of PD remains unclear, an array of evidence from the clinic and from
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