Basic NeuroscienceReviewα-Synuclein and nonhuman primate models of Parkinson's disease

- α-Synuclein (α-Syn) accumulation has a significant role in Parkinson's disease (PD).
- α-Syn protein sequence is well conserved across species.
- Nigral α-syn distribution in monkeys changes with age or toxin exposure.
- Viral vector gene transfer of wild type or mutated α-syn induces neurodegeneration.
- Novel PD monkey models are being generated using inoculations of α-syn and transgenesis.

Accumulation of α-synuclein (α-syn) leading to the formation of insoluble intracellular aggregates named Lewy bodies is proposed to have a significant role in Parkinson's disease (PD) pathology. Nonhuman primate (NHP) models of PD have proven essential for understanding the neurobiological basis of the disease and for the preclinical evaluation of first-in-class and invasive therapies. In addition to neurotoxin, aging and intracerebral gene transfer models, a new generation of models using inoculations of α-syn formulations, as well as transgenic methods is emerging. Understanding of their advantages and limitations will be essential when choosing a platform to evaluate α-syn-related pathology and interpreting the test results of new treatments targeting α-syn aggregation. In this review we aim to provide insight on this issue by critically analyzing the differences in endogenous α-syn, as well as α-syn pathology in PD and PD NHP models.