Both toxic and transgenic models are currently available for PD research. Toxic models are the classic – and oldest – experimental PD models and imply the use of compounds acting as mitochondrial toxins and/or proxidant agents, all provided with selective toxicity for dopaminergic neurons (i.e., MPTP, paraquat, rotenone, 6-hydroxydopamine, etc.). These compounds can be administered to the animals, mostly rodents or primates, either systemically or through stereotaxic injections directly into the nigrostriatal pathway (i.e. 6-hydroxydopamine). Depending on the compound and the route of administration, different sets of PD-like pathological and phenotypic features can be reproduced.
Transgenic models have become available more recently, with the advent of the “genetic era” of PD that followed the identification – in 1997 – of the first PD-linked mutation in the gene encoding for alpha-synuclein. The discovery of monogenic forms of PD has provided formidable insights into the disease pathogenesis, while the recent burst of genome-wide association studies has provided evidence that familial and sporadic forms of PD share common genetic backgrounds. These considerations have prompted the development of new animal models, rodents in particular, which recapitulate monogenic mutations, associated with toxic gain of function or loss of function in the gene product, observed in the major forms of autosomal dominant or recessive PD.
A list of the principal cell and animal PD models available is reported in the table available for download below.
Annex B of EXPERIMENTAL MODELS FOR NEURODEGENERATIVE DISEASES – Report of the JPND Action Group – January 2014 – from page 28 to page 33