Table 1.
The main animal models of Parkinson’s Disease (PD). The lack of full translatability renders preclinical research of PD still a challenge. To date, animal models are divided into three main groups: pharmacological, environmental and genetic. Although each model partially resembles PD features, the development of new experimental models would greatly contribute to our understanding in pathogenic mechanisms of PD.
| PD models | Type | Notes |
|---|---|---|
| Pharmacological | Reserpine | Induces transient parkinsonian symptoms without nigral dopaminergic neurodegeneration |
| Haloperidol |
Blocks striatal dopaminergic transmission |
|
| Environmental | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) | Widespread animal models. Rapid neurodegeneration does not mirror the chronic and progressive evolution of PD |
| 6-hydroxydopamine (6-OHDA) | ||
| Rotenone | Less frequently used models. Induce dopaminergic neuron loss and Lewy bodies. The main limitations are peripheral toxicity and extent inflammation | |
| Paraquat | ||
| Isoquinolines | ||
| Methamphetamine | ||
| Proteasome inhibitor I (PSI) | Induce nigrostriatal neuron loss and Lewy bodies with progressive motor disability. High variability and low reproducibility. | |
| Epoximicin | ||
| Lipopolysaccharide |
Induce inflammation and related nigrostriatal neuronal loss. Does not replicate PD features. |
|
| Genetic | Parkin | Knock-out mice for these genes show motor dysfunction, but no neurodegeneration |
| PTEN-induced kinase 1 (PINK1) | ||
| Protein deglycase (DJ-1) | ||
| Leucine-rich repeat kinase (LRRK) 2 | Knock-in mice show alteration of dopaminergic transmission, without clear behavioral deficits | |
| Vacuolar protein sorting-associated protein (VPS) 35 | Knock-out mice show a reduction in striatal dopamine level, accompanied by α-Synuclein accumulation and motor deficits | |
| Mitopark | The specific loss of the gene coding for mitochondrial transcription factor A in dopaminergic neurons leads to a progressive decline of neuronal function and slow development of PD-related behavior | |
| α-Synuclein models |
|