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Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Statins

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Background

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Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the prevention of these diseases. Research has found that statins are most effective for treating cardiovascular disease

Research

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1997

Pahan et al[1]

This study identified statin as an anti-inflammatory agent that suppressed the activation of NF-kappaB, expression of inducible nitric oxide synthase (iNOS), and cytokines (TNF-alpha, IL-1beta, and IL-6) in rat glial cells. This is the first report that describes the anti-neuroinflammatory properties of statin.


2008

Wolozin et al [2] obtained data for over 700,000 subjects taking simvastatin and over 50,000 subjects taking atorvastatin who were aged >64 years. Their findings were that:-

Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.


2008

Bar-On et al [3] carried out a study (in vitro) to determine if statins – cholesterol synthesis inhibitors – might interfere with α-synuclein accumulation in cellular models. Such accumulations (Lewy bodies( are a distinctive feature in the pathology of PD. Their findings:-

Statins reduced the levels of α-syn accumulation in the detergent insoluble fraction of the transfected cells. This was accompanied by a redistribution of α-syn in caveolar fractions, a reduction in oxidized α-syn, and enhanced neurite outgrowth. In contrast, supplementation of the media with cholesterol increased α-syn aggregation in detergent insoluble fractions of transfected cells and was accompanied by reduced neurite outgrowth.

2010

Ritz et al [4] evaluated the potential effect of statins on a cohort of PD patients in Denmark. Their conclusions:-

We found little evidence for a neuroprotective role of statins in PD except for short-term or high intensity users. Yet, further investigations into the contributions of intensity, duration, and lag periods of statin use may still be warranted.

Further Reading

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2011

Roy, Avik and Kalipada, Pahan Full Text Neuroscientist. 17(3): 244–255.

Prospects of Statins in Parkinson Disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132406/?tool=pmcentrez

Today

Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Statins.

This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.

Pubmed (abstracts)

Pubmed_Central (Full_Text)

Google_Scholar

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Therapy > Neuroprotection

Sub Pages:

Neuroprotective agents
Substances with possible neuroprotective properties:
Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--

References

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  1. ↑ Pahan, Kalipada; Sheikh, G. Faruq; Namboodiri, M.S. Aryan; Singh, I.(1997) Full Text Lovastatin and Phenylacetate Inhibit the Induction of Nitric Oxide Synthase and Cytokines in Rat Primary Astrocytes, Microglia, and Macrophages. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC508470/?tool=pmcentrez
  2. ↑ Wolozin, Benjamin; Wang, Stanley W.; Li, Nen-Chen; lee, Austin; Lee, Todd A. and Kazis, Lewis E. (2007) Full Text Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955446/?tool=pmcentrez
  3. ↑ Bar-On, Pazit; Crews, Leslie; Koob, Andrew O,; Mizuno, Hideya; Adame, Anthony, Spencer, Brian and Masliah, Eliezer (2008) Full Text J. Neurochem. 105(5): 1656. Statins reduce neuronal α-synuclein aggregation in in vitro models of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822545/?tool=pmcentrez
  4. ↑ Ritz, Beate; Manthripagada, Anglika D.; Qian, Lei; Schernhammer, Eva; Lene, Wermuth; Olsen, Jorgen and Soren, Friis (2010) Full Text Mov. Disord. 25(9): 1210–1216. Statin use and Parkinson’s disease in Denmark http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910157/?tool=pmcentrez
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