Non-steroidal anti-inflammatory drugs in Parkinson's disease

Abstract

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 upregulated 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 nigrostriatal 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.

Genome-wide association study confirms extant PD risk loci among the Dutch

“…46 In addition, the frequency of various HLA antigens was increased in patients with PD and in patients dying from postencephalitic PD. [53][54][55] Although PD is clearly not an autoimmune disorder, the occurrence of a localized attack of microglia during the disease course has been demonstrated with epidemiological, 56,57 animal model 58,59 and cell culture [60][61][62] approaches. Zhang et al 63 reported that aggregated a-synuclein activates microglia which, as a consequence, are toxic toward cultured dopaminergic neurons.…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…The hypothesis that inflammation may be related to the pathogenesis of PD has been derived from postmortem studies showing the presence of activated microglia cells and increased levels of inflammatory cytokines in substantia nigra and striatum [548][549][550][551]. A few studies also reported altered levels of serum inflammatory markers in PD patients [552][553][554].…”

“…Non-steroidal anti-inflammatory drugs (NSAIDs) protected against neuronal loss caused by MPTP in animals [551]. Based on this evidence, epidemiological studies have investigated the possible role of NSAIDs in PD.…”

MMHD [(S,E)-2-Methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a Novel Synthetic Compound Derived From Epothilone, Suppresses Nuclear Factor-κB–Mediated Cytokine Expression in Lipopolysaccharide-Stimulated BV-2 Microglia

“…Therefore, the inhibition of microglial activation could reduce neuronal cell death. In fact, a number of anti-inflammatory agents, which inhibit microglial activation or production of proinflammatory mediators under the central nervous system disease conditions, attenuate neuronal degeneration (35,36).…”