Entacapone and Tolcapone, Two Catechol-o-methyltransferase Inhibitors (icomt), Block Fibril Formation of Α-synuclein and Β-amyloid and Protect against Amyloid Induced Toxicity

Entacapone and Tolcapone, Two Catechol O-Methyltransferase Inhibitors, Block Fibril Formation of -Synuclein and -Amyloid and Protect against Amyloid-induced Toxicity*

Saviana Di Giovanni, Simona Eleuteri, Katerina E. Paleologou, Guowei Yin, Markus Zweckstetter , Pierre-Alain Carrupt**, and Hilal A. Lashuel From the Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology Lausanne, SV-BMI-LMNN-AI2351, CH-1015 Lausanne, Switzerland, the Dipartimento di Biologia Evoluzionistica Sperimentale, Università di Bologna Via Selmi...

Partial Peptide of α-Synuclein Modified with Small-Molecule Inhibitors Specifically Inhibits Amyloid Fibrillation of α-Synuclein

We have previously reported that pyrroloquinoline quinone (PQQ) prevents the amyloid formation of α-synuclein, amyloid β(1-42) (Aβ(1-42)), and mouse prion protein. Moreover, PQQ-modified α-synuclein and a proteolytic fragment of the PQQ-modified α-synuclein are able to inhibit the amyloid formation of α-synuclein. Here, we identified the peptide sequences that play an important role as PQQ-mod...

Synergistic inhibition of lung cancer cell lines by (-)-epigallocatechin-3-gallate in combination with clinically used nitrocatechol inhibitors of catechol-O-methyltransferase.

(-)-Epigallocatechin-3-gallate (EGCG) has exhibited been studied for lung cancer inhibitory activity in vitro and in animal models, but it is rapidly methylated and inactivated by catechol-O-methyltransferase (COMT). Entacapone and tolcapone, COMT inhibitors, are used to mitigate the symptoms of Parkinson's disease. We investigated the synergistic effects of entacapone/tolcapone and EGCG agains...

Comparison of the hepatic safety of catechol-O-methyltransferase inhibitors entacapone and tolcapone with special reference to uncoupling of oxidative phosphorylation

Elucidating Differences in the Hepatotoxic Potential of Tolcapone and Entacapone With DILIsym®, a Mechanistic Model of Drug‐Induced Liver Injury

Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors developed as adjunct therapies for treating Parkinson's disease. While both drugs have been shown to cause mitochondrial dysfunction and inhibition of the bile salt export protein (BSEP), liver injury has only been associated with the use of tolcapone. Here we used a multiscale, mechanistic model (DILIsym(®)) to simulat...