Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease of central nervous system. Despite many years of research its pathogenesis remains elusive. The main pathological process observed in PD is the degeneration of dopaminergic neurons in the substantia nigra and the reduction in the concentration of dopamine and its metabolites in the striatum and basal ganglia. In addition, a reduction in the activity of enzymes involved in the synthesis and metabolism of dopamine (e.g. tyrosine hydroxylase) is observed. The process of neurodegeneration is accompanied by the development of inflammatory reaction and the formation of intraneuronal inclusions - Lewy’s bodies, which containing mainly of α‑synuclein (ASN). The presence of ASN in Lewy bodies and the association of mutations in the gene encoding ASN with the familial form of the disease indicates the important role of this protein in the pathogenesis of PD.
ASN is a small protein widely distributed in the brain. Under physiological conditions it is involved, among others, in dopamine metabolism. Changes in ASN levels due to its aggregation, overexpression or decreased expression may disrupt dopaminergic system functions and contribute to the neurodegeneration process observed in PD.
Our paper is focused on murine ASN-based models of PD. In this review we describe models based on transgenic mice, viral vectors containing the ASN gene, and those in which elevated ASN levels are obtained by intracerebral protein administration. We briefly discuss the advantages of developed models and their numerous limitations We also highlight the need for further search for the ideal disease model.
Murine models of Parkinson’s disease caused by an increased concentration of α‑synuclein