Genetically engineered mouse models of Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting more than 1% of the population over age 60. The most common feature of PD is a resting tremor, though there are many systemic neurological effects, such as incontinence and sleep disorders. PD is histopathologically identified by the presence of Lewy bodies (LB), proteinaceous inclusions constituted primarily by α-synuclein. To date, there is no effective treatment to slow or stop disease progression. To help understand disease pathogenesis and identify potential therapeutic targets, many genetic mouse models have been developed. By far the most common of these models are the wildtype and mutant α-synuclein transgenic mice, because α-synuclein was the first protein shown to have a direct effect on PD pathogenesis and progression. There are many other gene-disrupted or -mutated models currently available, which are based on genetic anomalies identified in the human disease. In addition, there are also models which examine genes that may contribute to disease onset or progression but currently have no identified causative PD mutations. These genes are part of signaling pathways important for maintaining neuronal function in the nigrostriatal pathway. This review will summarize the most commonly used of the genetic mouse models currently available for PD research. We will examine how these models have expanded our understanding of PD pathogenesis and progression, as well as aided in identification of potential therapeutic targets in this disorder.

► Transgenic mouse models of wildtype and Parkinson's disease causing alpha-synuclein mutant genes expressed under different promoters.
► Transgenic and knockout mouse models of Parkinson's disease genes (PARKs).
► Other mouse models with genetic alterations in autophagy-lysosomal pathway, ubiquitin-proteasome pathway, monoamine metabolism and signaling, and mitochondrial biogenesis that are relevant to sporadic Parkinson's disease pathogenesis.
► Thoughts and comments have been given to the current model for Parkinson's disease pathogenesis and potential therapeutic strategies.