Table 1.
Representative neurotoxin-induced mammalian models of Parkinson's disease.
| Neurotoxin | Behavioral and pathological features | Molecular mechanisms |
|---|---|---|
| MPTP | (1) Parkinsonism (akinesia, rigidity, and tremor) with acute onset (2) Relatively less potent in rodents (3) Good response to L-DOPA and DA-agonists (4) Loss of TH-neurons (-fibers) and DA-content in nigrostriatal region (5) Loss of TH-neurons (-fibers) in ENS (6) α-Synuclein-positive inclusions (7) No typical LBs |
(1) Easily crosses the BBB (2) Converted to MPP+ in glial cells (3) Transferred into mitochondria by transporters (4) Inhibits electron transport chain complex I (5) Upregulation of iNOS, NADPH-oxidase, and ROS (6) Microglial activation |
| 6-OHDA | (1) Intracerebral administration (2) Quantifiable locomotor abnormalities (rotation, akinsesia) (3) Good response to L-DOPA and DA-agonists (4) Loss of TH-neurons (-fibers) and DA-content in nigrostriatal region (5) No typical LBs |
(1) Transferred into mitochondria by transporters (2) Inhibits electron transport chain complex I (3) Microglial activation |
| Rotenone | (1) Parkinsonism (bradykinesia, fixed posture, and rigidity) (2) Good response to L-DOPA and DA-agonists (3) Loss of TH-neurons (-fibers) and DA-content in nigrostriatal region (4) α-Synuclein-positive inclusions, resemblance to true LBs (5) Loss of myenteric neurons |
(1) Easily crosses the BBB (2) Inhibits electron transport chain complex I (3) Upregulation of NADPH-oxidase (4) Microglial activation |
| Paraquat (+ Maneb) | (1) Parkinsonism similar to that of induced by MPTP (2) Loss of DA-content in nigrostriatal region (3) α-Synuclein-positive inclusions with long exposure |
(1) Crosses the BBB by neutral amino acid transporter (2) Inhibits electron transport chain complex I (3) Reduction of nAchR-mediated DA release (4) Inhibits complex III (Maneb) |
MPTP: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 6-OHDA: 6-hydroxy-dopamine; L-DOPA: L-3,4-dihydroxy-L-phenylalanine; TH: tyrosine hydroxylase; DA: dopamine; ENS: enteric nervous system; LB: Lewy body; BBB: blood-brain barrier; MPP+: 1-methyl-4-phenylpyridinium; iNOS: inducible nitric oxide synthase; ROS: reactive oxygen species; nAchR: nicotinic acetylcholine receptor.