Paola Imbriani1, Giuseppe Sciamanna1, Massimo Santoro2, Tommaso Schirinzi3, Antonio Pisani4. 1. Neurology, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy; Fondazione Santa Lucia I.R.C.C.S., Laboratory of Neurophysiology and Plasticity, Rome, Italy. 2. Fondazione Don Gnocchi, Milano, Italy. 3. Neurology, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy. 4. Neurology, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy; Fondazione Santa Lucia I.R.C.C.S., Laboratory of Neurophysiology and Plasticity, Rome, Italy. Electronic address: pisani@uniroma2.it.
Abstract
BACKGROUND: In the past decade, the study of the pathogenic mechanisms underlying neurodegeneration in Parkinson's disease (PD) has revealed a genetic component, often associated with a number of environmental risk factors. Animal models have improved our understanding of disease pathogenesis, providing significant insights into the understanding of novel molecular pathways. Each model has its own specific features and limitations, and the choice of the most appropriate one depends on the specific question that has to be answered. AIM: To provide an overview of some of the models supporting the hypothesis that early synaptic dysfunction represents a central event in the course of the disease. DEVELOPMENT: Along with "classical" models, based on the administration of neurotoxins and capable of replicating the neuropathological hallmarks of the disease, a number of genetic models, reproducing the disease-causing mutations of monogenic forms of familial PD, have been generated. More recently, novel models have been developed, based on the combination of a toxic insult together with PD mutations, allowing for the identification of dysfunction at a prodromal disease stage. CONCLUSIONS: The development and characterization of new models is crucial for a better understanding of PD related-synaptopathy, and hold promise for the identification of novel therapeutics.
BACKGROUND: In the past decade, the study of the pathogenic mechanisms underlying neurodegeneration in Parkinson's disease (PD) has revealed a genetic component, often associated with a number of environmental risk factors. Animal models have improved our understanding of disease pathogenesis, providing significant insights into the understanding of novel molecular pathways. Each model has its own specific features and limitations, and the choice of the most appropriate one depends on the specific question that has to be answered. AIM: To provide an overview of some of the models supporting the hypothesis that early synaptic dysfunction represents a central event in the course of the disease. DEVELOPMENT: Along with "classical" models, based on the administration of neurotoxins and capable of replicating the neuropathological hallmarks of the disease, a number of genetic models, reproducing the disease-causing mutations of monogenic forms of familial PD, have been generated. More recently, novel models have been developed, based on the combination of a toxic insult together with PD mutations, allowing for the identification of dysfunction at a prodromal disease stage. CONCLUSIONS: The development and characterization of new models is crucial for a better understanding of PD related-synaptopathy, and hold promise for the identification of novel therapeutics.
Authors: Sarah M Hernandez; Elena B Tikhonova; Kristen R Baca; Fanpeng Zhao; Xiongwei Zhu; Andrey L Karamyshev Journal: Cells Date: 2021-10-18 Impact factor: 7.666
Authors: Roxana Braga de Andrade Teles; Tâmara Coimbra Diniz; Tiago Coimbra Costa Pinto; Raimundo Gonçalves de Oliveira Júnior; Mariana Gama E Silva; Érica Martins de Lavor; Antonio Wilton Cavalcante Fernandes; Ana Paula de Oliveira; Fernanda Pires Rodrigues de Almeida Ribeiro; Amanda Alves Marcelino da Silva; Taisy Cinthia Ferro Cavalcante; Lucindo José Quintans Júnior; Jackson Roberto Guedes da Silva Almeida Journal: Oxid Med Cell Longev Date: 2018-05-10 Impact factor: 6.543