Back and to the Future: From Neurotoxin-Induced to Human Parkinson's Disease Models

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Airavaara , M , Parkkinen , I , Konovalova , J , Albert , K , Chmielarz , P & Domanskyi , A 2020 , ' Back and to the Future: From Neurotoxin-Induced to Human Parkinson's Disease Models ' , Current Protocols in Neuroscience , vol. 91 , no. 1 , e88 . https://doi.org/10.1002/cpns.88

Title: Back and to the Future: From Neurotoxin-Induced to Human Parkinson's Disease Models
Author: Airavaara, Mikko; Parkkinen, Ilmari; Konovalova, Julia; Albert, Katrina; Chmielarz, Piotr; Domanskyi, Andrii
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2020-02-12
Language: eng
Number of pages: 33
Belongs to series: Current Protocols in Neuroscience
ISSN: 1934-8584
URI: http://hdl.handle.net/10138/318560
Abstract: Abstract 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.
Subject: alpha-synuclein
GWAS
neurotoxin
Parkinsonism
transgenesis
virus vector
3112 Neurosciences
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