Andis Klegeris1, Edith G McGeer, Patrick L McGeer. 1. Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada. aklegeri@interchange.ubc.ca
Abstract
PURPOSE OF REVIEW: According to the neuroinflammatory hypothesis of neurodegenerative diseases, drugs with an anti-inflammatory mode of action should slow the disease progression. Here we review recent advances in our understanding of one such disorder, Parkinson's disease, in which anti-inflammatory drugs are now becoming a new therapeutic focus. RECENT FINDINGS: The involvement of inflammatory mechanisms in Parkinson's disease has been revealed through in-vitro and in-vivo experimental studies supported by pathological and epidemiological findings. Several of the demonstrated inflammatory mechanisms are shared by other neurodegenerative disorders but some Parkinson's disease-specific mechanisms have also emerged. These include inflammatory stimulation by interaction of alpha-synuclein with microglia and astrocytes and a suppressive action by nonsteroidal anti-inflammatory drugs on dopamine quinone formation. SUMMARY: It can be anticipated that a more detailed understanding of neuroinflammatory mechanisms in Parkinson's disease will lead to new cellular and molecular targets, which may, in turn, permit design of Parkinson's disease modifying drugs. Future treatment may involve combination therapies with drugs directed at both inflammatory and non-inflammatory mechanisms.
PURPOSE OF REVIEW: According to the neuroinflammatory hypothesis of neurodegenerative diseases, drugs with an anti-inflammatory mode of action should slow the disease progression. Here we review recent advances in our understanding of one such disorder, Parkinson's disease, in which anti-inflammatory drugs are now becoming a new therapeutic focus. RECENT FINDINGS: The involvement of inflammatory mechanisms in Parkinson's disease has been revealed through in-vitro and in-vivo experimental studies supported by pathological and epidemiological findings. Several of the demonstrated inflammatory mechanisms are shared by other neurodegenerative disorders but some Parkinson's disease-specific mechanisms have also emerged. These include inflammatory stimulation by interaction of alpha-synuclein with microglia and astrocytes and a suppressive action by nonsteroidal anti-inflammatory drugs on dopamine quinone formation. SUMMARY: It can be anticipated that a more detailed understanding of neuroinflammatory mechanisms in Parkinson's disease will lead to new cellular and molecular targets, which may, in turn, permit design of Parkinson's disease modifying drugs. Future treatment may involve combination therapies with drugs directed at both inflammatory and non-inflammatory mechanisms.
Authors: Alena V Savonenko; Tatiana Melnikova; Andrew Hiatt; Tong Li; Paul F Worley; Juan C Troncoso; Phil C Wong; Don L Price Journal: Neuropsychopharmacology Date: 2011-09-21 Impact factor: 7.853
Authors: Ashley D Reynolds; Irena Kadiu; Sanjay K Garg; Jason G Glanzer; Tara Nordgren; Pawel Ciborowski; Ruma Banerjee; Howard E Gendelman Journal: J Neuroimmune Pharmacol Date: 2008-01-17 Impact factor: 4.147