Format

Send to

Choose Destination
Curr Protoc Neurosci. 2020 Mar;91(1):e88. doi: 10.1002/cpns.88.

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

Author information

1
Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland.
2
Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
3
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
4
Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

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.

KEYWORDS:

GWAS; Parkinsonism; alpha-synuclein; neurotoxin; transgenesis; virus vector

PMID:
32049438
DOI:
10.1002/cpns.88

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center