Abstract
Neuroinflammation in Parkinson's disease (PD) is a chronic process that is associated with alteration of glial cells, including astrocytes and microglia. However, the precise mechanisms remain obscure. To better understand neuroinflammation in PD, we focused on glial activation in α-synuclein (αS) transgenic and related model mice. In the majority of αS transgenic mice, astrogliosis was observed concomitantly with accumulation of αS during the early stage of neurodegeneration. However, microglia were not extensively activated unless the mice were treated with lipopolysaccharides or through further genetic modification of other molecules, including familial PD risk factors. Thus, the results in αS transgenic mice and related model mice are consistent with the idea that neuroinflammation in PD is a double-edged sword that is protective in the early stage of neurodegeneration but becomes detrimental with disease progression.
Highlights
The neurodegenerative brain in Parkinson’s disease (PD) is characterized by protein aggregation of α-synuclein, formation of Lewy bodies and Lewy neuritis, extensive loss of dopaminergic neurons, and gliosis in the substantia nigra [1, 2]
Similar αS pathologies have been observed in various types of α-synucleinopathies, including Dementia with Lewy Bodies (DLB), multiple system atrophy (MSA), neurodegeneration with brain iron accumulation, type 1, and the Lewy body variant of Alzheimer’s disease (AD) [2]
Since the single nucleotide polymorphism (SNP) of leucine-rich repeat kinase 2 (LRRK2) and Parkin that are positively linked to inflammatory bowel diseases and leprosy differ from those linked to PD [7, 8], it is unclear whether the molecular mechanisms are similar in α-synucleinopathies and other inflammation-related disorders
Summary
The neurodegenerative brain in Parkinson’s disease (PD) is characterized by protein aggregation of α-synuclein (αS), formation of Lewy bodies and Lewy neuritis, extensive loss of dopaminergic neurons, and gliosis in the substantia nigra [1, 2]. In addition to cell-autonomous neurotoxicity due to aggregation of αS, mounting evidence from histology and cell biology has suggested that non-cell-autonomous neuroinflammation may be crucial for neurotoxicity since aberrant activation of glial cells may stimulate inflammation, leading to neuronal cell death [5, 6]. This view has been supported by recent progress in genetic studies. The main objective of this paper is to explore the mechanism of neuroinflammation based on information derived from transgenic (tg) mouse models of α-synucleinopathies
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