Clinical Studies and Therapies in Parkinson's Disease: Translations from Preclinical Models

Description

More than 50 years have passed since the use of L-dopa in the palliative treatment of Parkinson’s disease, but it remains the most common treatment despite inducing severe side effects such as dyskinesia after 4–6 years of use. Numerous preclinical investigations based on endogenous neurotoxin models have promised various therapies for Parkinson’s disease, but these efforts have failed when attempting to transfer these successful results to preclinical studies. Although several publications have warned of these failures, the scientific community remains mostly unaware, and there is a need to focus their efforts on potential therapeutics that can slow or halt development of the disease. Clinical Studies and Therapies in Parkinson’s Disease: Translations from Preclinical Models analyzes preclinical models based on exogenous neurotoxins and why they have failed. Neuroscientists, neurologists, and neuropharmacologists will benefit greatly from the book’s discussion of these newer models, their benefits, and the need for their implementation. This book also provides the basic concepts of dopamine metabolism for students taking courses in neurochemistry, neuroscience, neuropharmacology, biochemistry, and medicine. Front Cover CLINICAL STUDIES AND THERAPIES IN PARKINSON’S DISEASE Clinical Studies and Therapies in Parkinson’s DiseaseTranslations from Preclinical Models Copyright Dedication Contents 1 - Parkinson's disease A. Epidemiology References B. Parkinson's disease classification C. Parkinsonism D. Idiopathic Parkinson’s disease References E. Genetic Parkinson's disease 2 - Parkinson's pharmacological therapy Dopaminergic drugs l-dopa Dopamine agonists Monoamine oxidase inhibitors Anticholinergic drugs Other pharmacological treatments New targets and disease-modifying drugs for Parkinson's disease treatment in phase 3 Adenosine antagonists Glucagon-like peptide-1 receptor agonists Memantine Ganoderma lucidum Drugs in clinical trials References 3 - Dopamine synthesis Tyrosine hydroxylase Aromatic amino acid decarboxylase References 4 - Dopamine storage and release References 5 - Dopamine oxidative deamination Monoamine oxidases Monoamine oxidase-B References 6 - Dopamine methylation Catechol ortho-methyltransferase References 7 - Dopamine oxidation to neuromelanin and neurotoxic metabolites Dopamine ortho-quinone Aminochrome 5,6-Indolequinone Dopaminochrome Neuromelanin References 8 - Neuroprotective mechanisms against dopamine oxidation-dependent neurotoxicity Vesicular monoamine transporter-2 DT-diaphorase Glutathione transferase-M2-2 Astrocytes neuroprotection against aminochrome neurotoxicity References 9 - Exogenous neurotoxins as a preclinical model for Parkinson's disease 6-Hydroxydopamine 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Rotenone Exogenous neurotoxin preclinical models for Parkinson's disease References 10 - Preclinical models based on genetic mutations associated with the familial form of Parkinson's disease References 11 - Preclinical models based on endogenous neurotoxins Alpha-synuclein Alpha-synuclein aggregation and accumulation in Lewy bodies Alpha-synuclein aggregation to neurotoxic oligomers inside dopaminergic neurons of nigrostriatal system 3,4-Dihydroxyphenylacetaldehyde Aminochrome References 12 - Conclusions Index A B C D E F G H I K L M N O P R S T U V W X Y Back Cover