Parkinson's Disease Tulip


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Old 03-10-2010, 06:29 PM #1
paula_w paula_w is offline
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paula_w paula_w is offline
In Remembrance
 
Join Date: Aug 2006
Location: Florida
Posts: 3,904
15 yr Member
Default stalevo

i just started on stalevo today - might have been a good move according to this article...entacapone and tolcapone may protect people from beta-amyeloid build up and excess alpha synuclein.


J Biol Chem. 2010 Feb 11. [Epub ahead of print]

Entacapone and Tolcapone, two catechol-O-methyltransferase inhibitors (ICOMT), block fibril formation of {alpha}-synuclein and {beta}-amyloid and protect against amyloid-induced toxicity.
Di Giovanni S, Eleuteri S, Paleologou KE, Yin G, Zweckstetter M, Carrupt PA, Lashuel HA.

Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland;

Parkinsons disease (PD) is the second most common neurodegenerative disorder after Alzheimers disease (AD). There is considerable consensus that the increased production and/or aggregation of alpha-synuclein play a central role in the pathogenesis of in PD and related synucleinopathies. Current therapeutic strategies for treating PD offer mainly transient symptomatic relief and aim at the restitution of dopamine levels to counterbalance the loss of dopaminergic neurons. Therefore, the identification and development of druglike molecules that block alpha-synuclein aggregation and prevent the loss of dopaminergic neurons is desperately needed to treat or slow the progression of PD. Herein, we show that entacapone (E) and tolcapone (T), already approved as adjunct drugs in the therapy of PD, are potent inhibitors of alpha-synuclein and Abeta oligomerization and fibrillogensis and protect against extracellular toxicity induced by the aggregation of both proteins. Comparison of the anti-aggregation properties of entacapone and tolcapone with the effect of six other catechol containing compounds, dopamine, pirogallol, gallic acid, caffeic acid and quercetin on the oligomerization and fibrillization of alpha-synuclein and Abeta demonstrate that the catechol moiety is essential for the anti-amyoidogenic activity. Our studies present the first characterization of the antiamyloidogenic properties of Tolcapone and Entacapone against both alpha-synuclein and Abeta42 fibrillization and highlight the potential of this class of nitro-catechol compounds as anti-amyloidogenic agents. Their inhibitory properties, mode of action and structural properties suggest that they constitute promising lead compounds for further optimization.

PMID: 20150427 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20150427
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