Non-steroidal anti-inflammatory drugs in Parkinson's disease.
Parkinson's disease (PD) is known to be a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of experimental evidence indicates that the factors involved in the pathogenesis of this disease are several, occurring inside and outside the DAergic neuron. Recently, the role of the neuron-glia interaction and the inflammatory process, in particular, has been the object of intense study by the research community. It seems to represent a new therapeutic approach opportunity for this neurological disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-2) is up-regulated in SNc DAergic neurons in both PD patients and animal models of PD and, furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) pre-treatment protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 hydroxydopamine (6-OHDA)-induced nigro-striatal dopamine degeneration. Moreover, recent epidemiological studies have revealed that the risk of developing PD is reduced in humans who make therapeutical use of NSAIDs. Consequently, it is hypothesized that they might delay or prevent the onset of PD. However, whether or not these common drugs may also be of benefit to those individuals who already have Parkinson's disease has not as yet been shown. In this paper, evidence relating to the protective effects of aspirin or other NSAIDs on DAergic neurons in animal models of Parkinson's disease will be discussed. In addition, the pharmacological mechanisms by which these molecules can exert their neuroprotective effects will be reviewed. Finally, epidemiological data exploring the effectiveness of NSAIDs in the prevention of PD and their possible use as adjuvants in the therapy of this neurodegenerative disease will also be examined.
Esposito
Ennio
E
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Di Matteo
Vincenzo
V
Benigno
Arcangelo
A
Pierucci
Massimo
M
Crescimanno
Giuseppe
G
Di Giovanni
Giuseppe
G
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008875:Middle Aged; D018696:Neuroprotective Agents; D010300:Parkinson Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents