Oxidative stress and synaptic dysfunction in rodent models of Parkinson's disease

Parkinson's disease (PD) is a multifactorial disorder involving a complex interplay between a variety of genetic and environmental factors. In this scenario, mitochondrial impairment and oxidative stress are widely accepted as crucial neuropathogenic mechanisms, as also evidenced by the identification of PD-associated genes that are directly involved in mitochondrial function. The concept of mitochondrial dysfunction is closely linked to that of synaptic dysfunction. Indeed, compelling evidence supports the role of mitochondria in synaptic transmission and plasticity, although many aspects have not yet been fully elucidated. Here, we will provide a brief overview of the most relevant evidence obtained in different neurotoxin-based and genetic rodent models of PD, focusing on mitochondrial impairment and synaptopathy, an early central event preceding overt nigrostriatal neuro -degeneration. The identification of early deficits occurring in PD pathogenesis is crucial in view of the devel-opment of potential disease-modifying therapeutic strategies.

Automated summary

Parkinson's disease (PD) is a multifactorial disorder with genetic and environmental factors playing a part. Mitochondrial impairment and oxidative stress are important mechanisms in PD, supported by PD-associated genes involved in mitochondrial function. Dysfunction of mitochondria is closely linked to synaptic dysfunction, which is an early event before nigrostriatal neurodegeneration in PD.