More than 50 years have passed since the use of L-dopa in the palliative treatment of Parkinson's Disease, and it remains as the most common treatment despite the fact that after 4-6 years it induces severe side effects such as dyskinesia. Numerous preclinical investigations based on endogenous neurotoxin models have promised various therapies in Parkinson's disease, but efforts have failed at the time of transferring these successful results to preclinical studies. Although there are several publications that warn of these failures, the scientific community remains mostly unaware, and there is a need to focus their efforts on potential therapeutics that can slow the development of the disease.
Translation of Preclinical Models to Clinical Studies and Therapies in Parkinson's Disease: Translations from Preclinical Models analyses why preclinical models based on exogenous neurotoxins have failed. To develop new pharmacological treatments for Parkinson´s Disease, the book discusses a more physiological model directly related to metabolism of dopaminergic neurons that are lost before and after the onset of the disease. This book also reviews genetic preclinical models based on genetic mutations associated with the familial form of the disease and preclinical models based on endogenous neurotoxins.
- Analyses why preclinical models of Parkinson's Disease therapies based on exogenous neurotoxins have failed
- Proposes a more physiological model directly related to metabolism of dopaminergic neurons
- Reviews genetic preclinical models based on genetic mutations and preclinical models based on endogenous neurotoxins
2. Parkinson´s pharmacological therapy
3. Dopamine Synthesis
4. Dopamine storage and release
5. Dopamine oxidative deamination
6. Dopamine methylation
7. Dopamine oxidation to neuromelanin and neurotoxic metabolites
8. Neuroprotective mechanisms against dopamine oxidation-dependent neurotoxicity
9. Preclinical model based on exogenous neurotoxins for Parkinson's disease
10. Preclinical models based on genetic mutations associated with the familial form of Parkinson´s disease
11. Preclinical models based on endogenous neurotoxins
Dr. Juan Segura-Aguilar, Ph.D. is a professor of molecular and clinical pharmacology at the University of Chile, Santiago, Chile. He obtained his PhD in biochemistry from Stockholm University, Stockholm, Sweden in 1989. He was previously an associate professor at Uppsala University, Uppsala, Sweden. In 1998, he started as an associate professor at University of Chile, and since 2001 has been a full professor. His research has been focused on mechanisms involved in dopaminergic neurons degeneration in Parkinson´s disease. He has over 140 publications on neurodegeneration research.