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

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An under-researched drug,which shows considerable promise.

Background

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Celastrol is a form of quinone methide, It is a plant-derived triterpene used in Chinese medicine, which is extracted from the root bark of an ivy-like, creeping plant called Triperygium wilfordii (TW) that is indigenous to Southern China. Extracts of the plant have had a long history of use in traditional Chinese medicine for treating fever, chills, edema and joint pain, conditions commonly associated with inflammation. It works by suppressing microglial cell activation, the release of the inflammatory cytokines TNF-α and IL-1β by human macrophages and monocytes, and the production of nitric oxide (NO) by iNOS.

Research

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2005

Cleren et al [1] evaluated this drug, which is derived from a perennial creeping plant belonging to the Celastraceae family.

Mice were treated with celastrol before and after injections of MPTP, a dopaminergic neurotoxin, which produces a model of PD. A 48% loss of dopaminergic neurons induced by MPTP in the substantia nigra pars compacta was significantly attenuated by celastrol treatment. Moreover, celastrol treatment significantly reduced the depletion in dopamine concentration induced by MPTP.


2007

Corson and Crews [2] reviewed a number of traditional medicines:-

Although not yet tested as a single agent in humans, celastrol has shown promise as an anti-inflammatory compound in animal models of arthritis, lupus, amyotrophic lateral sclerosis, and Alzheimer’s disease It also has antiproliferative effects against numerous cancer cell lines.


2009

Faust et al [3] reported on a series of tests on fruit flies.

In the present study, a Drosophila DJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10), and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX). All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection in Drosophila DJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level.

Further Reading

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2001


Allison, A. C.; Cacabelos R.; Lombardi, V. R.; Alvarez, X. A. and Vigo, C. Abstract Prog. Neuropsychopharmacol Biol. Psychiatry. 25 (7):1341 - 1357.

Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/11513350

2011

Fakhari, Darius Ebrahimi; Wahlster, Lara and McLean, Pamela J. Full Text J. Parkinsons Dis. 1 (4): 299–320.

Molecular Chaperones in Parkinson’s Disease – Present and Future

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264060/?tool=pmcentrez


2012

Description by Cayman Chemicals.

http://www.caymanchem.com/app/template/Product.vm/catalog/70950


Description by Enzo Life Sciences

http://www.enzolifesciences.com/ALX-350-332/celastrol/


Today

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

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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<references>

  1. Cleren C.; Calingasan, N. Y.; Chen, J. and Beal M. F. (2005) Abstract J. Neurochem. 94 (4):995-1004. Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity. http://www.ncbi.nlm.nih.gov/pubmed/16092942?dopt=Citation#
  2. Corson, Timothy W. and Crews. Craig M. (2007) Full Text Cell 130 (5) 769 – 774. Molecular Understanding and Modern Application of Traditional Medicines: Triumphs and Trials http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2507744/?tool=pmcentrez
  3. Faust, K,; Gehrke, S.; Yang, Y.; Yang, L.; Beal M. F. and Lu, B. (2009) Full Text BMC Neurosci. Sep 1;10:109. Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152779/?tool=pmcentrez