Therapeutic approaches to inflammation in neurodegenerative disease.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Klegeris
Andis
A
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada. aklegeri@interchange.ubc.ca
McGeer
Edith G
EG
McGeer
Patrick L
PL
D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D004660:Encephalitis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D005911:Gliosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods / Q000639:trends*; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D018121:Receptors, Cytokine / Q000187:drug effects / Q000276:immunology; D051844:alpha-Synuclein / Q000276:immunology
D007155:Immunologic Factors; D018121:Receptors, Cytokine; D051844:alpha-Synuclein