Therapeutic strategies in Parkinson's disease: what we have learned from animal models

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra, as well as in other brain areas. The currently available dopamine replacement therapy provides merely symptomatic benefit and is ineffective because habituation and side effects arise relatively quickly. Studying the genetic forms of PD in animal models provides novel insight that allows targeting of specific aspects of this heterogenic disease more specifically. Among others, two important cellular deficits are associated with PD; these deficits relate to (1) synaptic transmission and vesicle trafficking, and (2) mitochondrial function, relating respectively to the dominant and recessive mutations in PD-causing genes. With increased knowledge of PD, the possibility of identifying an efficient, long-lasting treatment is becoming more conceivable, but this can only be done with an increased knowledge of the specific affected cellular mechanisms. This review discusses how discoveries in animal models of PD have clarified the therapeutic potential of pathways disrupted in PD, with a specific focus on synaptic transmission, vesicle trafficking, and mitochondrial function.