Elsevier

Progress in Neurobiology

Volume 89, Issue 3, November 2009, Pages 277-287
Progress in Neurobiology

The influence of microglia on the pathogenesis of Parkinson's disease

https://doi.org/10.1016/j.pneurobio.2009.08.001Get rights and content

Abstract

Parkinson's disease (PD) is characterised by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Inflammation may be associated with the neuropathology of PD due to the following accumulating evidence: excessive microglial activation and increased levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-1β in the SNpc of patients with PD; the emergence of PD-like symptoms following influenza infection; the increased susceptibility to PD associated with bacterial vaginosis; the presence of inflammatory mediators and activators in animal models of PD; the ability of anti-inflammatory drugs to decrease susceptibility to PD; and the emerging possibility of the use of microglial activation inhibitors as a therapy in PD. In this review, we will discuss the role of inflammation in PD. We will focus on the influence of microglia in the pathogenesis of PD and discuss potential therapeutic interventions for PD, that target microglia.

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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