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Curr Protoc Neurosci ; 91(1): e88, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32049438

RESUMEN

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by motor symptoms such as tremor, slowness of movement, rigidity, and postural instability, as well as non-motor features like sleep disturbances, loss of ability to smell, depression, constipation, and pain. Motor symptoms are caused by depletion of dopamine in the striatum due to the progressive loss of dopamine neurons in the substantia nigra pars compacta. Approximately 10% of PD cases are familial arising from genetic mutations in α-synuclein, LRRK2, DJ-1, PINK1, parkin, and several other proteins. The majority of PD cases are, however, idiopathic, i.e., having no clear etiology. PD is characterized by progressive accumulation of insoluble inclusions, known as Lewy bodies, mostly composed of α-synuclein and membrane components. The cause of PD is currently attributed to cellular proteostasis deregulation and mitochondrial dysfunction, which are likely interdependent. In addition, neuroinflammation is present in brains of PD patients, but whether it is the cause or consequence of neurodegeneration remains to be studied. Rodents do not develop PD or PD-like motor symptoms spontaneously; however, neurotoxins, genetic mutations, viral vector-mediated transgene expression and, recently, injections of misfolded α-synuclein have been successfully utilized to model certain aspects of the disease. Here, we critically review the advantages and drawbacks of rodent PD models and discuss approaches to advance pre-clinical PD research towards successful disease-modifying therapy. © 2020 The Authors.


Asunto(s)
Neurotoxinas/toxicidad , Trastornos Parkinsonianos , Animales , Cuerpo Estriado/efectos de los fármacos , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/ultraestructura , Evaluación Preclínica de Medicamentos/métodos , Predicción , Estudio de Asociación del Genoma Completo , Técnicas Histológicas , Humanos , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/genética , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/genética , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/patología , Plaguicidas/toxicidad , Agregación Patológica de Proteínas/genética , Agregación Patológica de Proteínas/patología , Ratas , Sustancia Negra/efectos de los fármacos , Sinucleinopatías/genética , Sinucleinopatías/patología , alfa-Sinucleína/biosíntesis , alfa-Sinucleína/genética
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