By Elżbieta Lorenc-Koci (auth.), Lucyna Antkiewicz-Michaluk, Hans Rommelspacher (eds.)
the explicit subject, “Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants – New views In Parkinson`S ailment Therapy,” used to be selected in mild of gathering neurobiological facts indicating that, as well as exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]), endogenous compounds could play a major position within the commonest neurodegenerative problems (e.g., Parkinson`s disease). teams of amine similar compounds, which seemed chemically like MPTP, have been detected in human mind and cerebrospinal fluid (CSF): ß-carbolines (BCs) and tetrahydroisoquinolines (TIQs). those are heterocyclic compounds shaped endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a large spectrum of psychopharmacological and behavioral results. The TIQs and BCs could bind to their very own excessive affinity websites on neuronal membranes linked to or positioned with regards to the receptors of neurotransmitters. learn on TIQs and BCs is motivated additionally by way of their attainable function in pathological stipulations, particularly parkinsonism and alcoholism. lately, scientific curiosity has been spurred by way of their position as neuroprotective, or even neurorestorative, anticonvulsant and antiaddictive, components.
In this ebook we will summarize, for the 1st time, the consequences from behavioral, neurochemical and molecular experiments, which show a large spectrum of TIQs and BCs results - from their particularly light neurotoxic activities to the $64000 neuroprotective and antiaddictive homes.
Additionally, the hot result of experimental reports in vivo have allowed a more robust realizing and simultaneous comparability of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic activities of endogenous TIQs and BCs and feature pointed to the opportunity of their healing purposes in neurodegenerative illnesses corresponding to Parkinson's disease.
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Extra resources for Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants: New Vistas In Parkinson's Disease Therapy
Neurosci Lett 266:149–151 Borges CR, Geddes T, Watson JT, Kuhn DM (2002) Dopamine biosynthesis is regulated by S-glutathionylation. Potential mechanism of tyrosine hydroxylast inhibition during oxidative stress. J Biol Chem 277:48295–48302 Bradbury AJ, Costall B, Domeney AM, Testa B et al (1985) The toxic actions of MPTP and its metabolite MPP+ are not mimicked by analogues of MPTP lacking an N-methyl moiety. Neurosci Lett 61:121–126 Bradbury AJ, Costall B, Domeney AM, Jenner P (1986) 1-methyl-4-phenylpyridine is neurotoxic to the nigrostriatal dopamine pathway.
1996; Chan 1998; Dykens 1999). At the same time, 1BnTIQ significantly inhibits the COMT-dependent O-methylation pathway. Striatum and nucleus accumbens represent brain regions where the depression of dopamine produced by 1BnTIQ is most powerfully expressed, this effect being specific to dopaminergic neurons. The biochemical effects of the chronic 38 A. Wąsik and L. Antkiewicz-Michaluk administration of 1BnTIQ are considerably weaker. This pattern of changes suggests that during chronic 1BnTIQ administration some tolerance to its dopaminedepressing effect develops, while the impairment of dopamine synthesis ensues (Wąsik et al.
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