Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease
ABSTRACT Markers of neuroinflammation, including activated microglia and increased levels of circulating proinflammatory cytokines, have been observed in the brains and CSF of patients with Parkinson disease (PD). Yet the link between anti-inflammatory agents and PD in humans remains uncertain, despite indications that neuroinflammation may contribute to cell death in the PD brain and experimental evidence of anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) exerting neuroprotective effects in animal models.
Using a population-based approach, we studied NSAID use among 293 incident idiopathic PD cases and 286 age-, race-, and gender-matched controls from three rural California counties.
Our data suggested a decreased risk of PD among regular (>or=2 pills/week for at least 1 month) aspirin NSAID users (OR, 0.80; 95% CI, 0.56 to 1.15). A stronger protective effect was observed for regular nonaspirin NSAID users (OR, 0.52; 95% CI, 0.35 to 0.79), particularly those who reported 2 or more years of use (OR, 0.44; 95% CI, 0.26 to 0.74). The aspirin effect estimates differed by gender, showing a protective effect only in women, especially among long term (>or=24 months) regular users (OR, 0.51; 95% CI, 0.26 to 1.02).
Our study contributes to the growing body of literature suggesting a protective role for nonsteroidal anti-inflammatory drugs (NSAIDs) in Parkinson disease (PD). Given our results and the biologic plausibility of a neuroprotective function for NSAIDs there is a pressing need for further studies elucidating the protective role such drugs may play in PD.
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- "Published literature on AD and PD includes robust evidence of disturbances in inflammation and immune pathways. Increased levels of pro-inflammatory cytokines are common findings in blood, cerebrospinal fluid (CSF), and post-mortem brain tissue in both diseases    , and non-steroidal anti-inflammatory drugs have been proposed to have protective effects  . Active debate has endured on whether inflammation and immune dysregulation are contributors to neurodegeneration or are instead secondary to ongoing cell death. "
ABSTRACT: The discovery of causative genetic mutations in affected family members has historically dominated our understanding of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Nevertheless, most cases of neurodegenerative disease are not explained by Mendelian inheritance of known genetic variants, but instead are thought to have a complex etiology with numerous genetic and environmental factors contributing to susceptibility. Although unbiased genome-wide association studies (GWAS) have identified novel associations to neurodegenerative diseases, most of these hits explain only modest fractions of disease heritability. In addition, despite the substantial overlap of clinical and pathologic features among major neurodegenerative diseases, surprisingly few GWAS-implicated variants appear to exhibit cross-disease association. These realities suggest limitations of the focus on individual genetic variants and create challenges for the development of diagnostic and therapeutic strategies, which traditionally target an isolated molecule or mechanistic step. Recently, GWAS of complex diseases and traits have focused less on individual susceptibility variants and instead have emphasized the biological pathways and networks revealed by genetic associations. This new paradigm draws on the hypothesis that fundamental disease processes may be influenced on a personalized basis by a combination of variants - some common and others rare, some protective and others deleterious - in key genes and pathways. Here, we review and synthesize the major pathways implicated in neurodegeneration, focusing on GWAS from the most prevalent neurodegenerative disorders, AD and PD. Using literature mining, we also discover a novel regulatory network that is enriched with AD- and PD-associated genes and centered on the SP1 and AP-1 (Jun/Fos) transcription factors. Overall, this pathway- and network-driven model highlights several potential shared mechanisms in AD and PD that will inform future studies of these and other neurodegenerative disorders. These insights also suggest that biomarker and treatment strategies may require simultaneous targeting of multiple components, including some specific to disease stage, in order to assess and modulate neurodegeneration. Pathways and networks will provide ideal vehicles for integrating relevant findings from GWAS and other modalities to enhance clinical translation.01/2013; 2(3):145-175.
Neurodegeneration, 04/2012; , ISBN: 978-953-51-0502-2
- "NSAIDs have been associated with a 45% reduction in the risk of developing PD in one prospective study with 14 years of follow up (Wahner et al., 2007). On the other hand a case control study of 22,007 patients did not find evidence that NSAIDs use reduces PD (Driver et al., 2011). "
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- "November 2011 | Volume 2 | Article 68 | 5 Seidl and Potashkin Neuroprotection in Parkinson's disease 2006; Wahner et al., 2007; Gao et al., 2011 "
ABSTRACT: Parkinson's disease (PD) is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction, and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline, and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.Frontiers in Neurology 11/2011; 2:68. DOI:10.3389/fneur.2011.00068