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Strategic Selection of Neuroinflammatory Models in Parkinson's Disease: Evidence from Experimental Studies

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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.
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Keywords: 1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine; Experimental models; Parkinson’s disease; microglia; neurodegeneration; neuroinflammation

Document Type: Research Article

Publication date: August 1, 2013

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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