Title:Strategic Selection of Neuroinflammatory Models in Parkinson's Disease: Evidence from Experimental Studies
Volume: 12
Issue: 5
Author(s): Sandeep Vasant More, Hemant Kumar, In-Su Kim, Sushruta Koppulla, Byung-Wook Kim and Dong-Kug Choi
Affiliation:
Keywords:
Experimental models, microglia, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, neurodegeneration,
neuroinflammation, Parkinson’s disease.
Abstract: Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the
substantia nigra pars compacta (SNpc). Although the exact cause of the dopaminergic neurodegeneration remains elusive,
recent postmortem and experimental studies have revealed a crucial role of neuroinflammation that is initiated and driven
by activated microglial cells and their neurotoxic products during PD pathogenesis. Inflammatory responses manifested
by glial reactions are currently recognized as one of the prominent features of PD. Indeed, activated microglial cells have
been detected in the SNpc of patients with PD. Postmortem analysis and preclinical investigations conducted in various
animal models exposed to neurotoxins have also revealed dramatic and massive astrogliosis with the presence of activated
microglial cells in the SNpc. Although a number of neurotoxic, pharmacologic, and transgenic animal models are
available for mechanistic and drug discovery studies in PD, selection and use of a good experimental PD model has
always been a challenge. Significant advances in modeling neuroinflammatory features and expansion to new species
have occurred to better characterize the pathological mechanisms in PD. Here, we outline the remarkable array of animal
and cellular neuroinflammatory models available, with particular emphasis on their benefits and pitfalls and the
contribution each has made to delineate the neuroinflammatory mechanisms underlying PD. This review suggests that
further investigation concerning use of optimal neuroinflammatory experimental PD models might help to identify
disease-modifying therapeutic approaches in future drug discovery and may shed light on understanding PD pathogenesis.
