Peroxisome Proliferator-Activated Receptor-γ in Amyotrophic Lateral Sclerosis and Huntington's Disease
نویسنده
چکیده
Amyotrophic lateral sclerosis (ALS) is a debilitating and one of the most common adult-onset neurodegenerative diseases with the prevalence of about 5 per 100 000 individuals. It results in the progressive loss of upper and lower motor neurons and leads to gradual muscle weakening ultimately causing paralysis and death. ALS has an obscure cause and currently no effective treatment exists. In this review, a potentially important pathway is described that can be activated by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists and has the ability to block the neuropathological damage caused by inflammation in ALS and possibly in other neudegenerative diseases like Huntington's disease (HD). Neuroinflammation is a common pathological feature in neurodegenerative diseases. Therefore, PPAR-gamma agonists are thought to be neuroprotective in ALS and HD. We and others have tested the neuroprotective effect of pioglitazone (Actos), a PPAR-gamma agonist, in G93A SOD1 transgenic mouse model of ALS and found significant increase in survival of G93A SOD1 mice. These findings suggest that PPAR-gamma may be an important regulator of neuroinflammation and possibly a new target for the development of therapeutic strategies for ALS. The involvement of PPAR-gamma in HD is currently under investigation, one study finds that the treatment with rosiglitazone had no protection in R6/2 transgenic mouse model of HD. PPAR-gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that works together with combination of other transcription factors like PPAR-gamma in the regulation of mitochondrial biogenesis. Therefore, PPAR-gamma is a possible target for ALS and HD as it functions as transcription factor that interacts with PGC-1alpha. In this review, the role of PPAR-gamma in ALS and HD is discussed based on the current literature and hypotheses.
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ورودعنوان ژورنال:
- PPAR Research
دوره 2008 شماره
صفحات -
تاریخ انتشار 2008