Postmortem studies using the PD brain reported extensive microgliosis in the brain regions affected by synuclein pathology ( Brás et al., 2020 Harms et al., 2020). In addition to αSyn propagation, neuroinflammation has been suggested as one of the main mechanisms contributing to PD pathogenesis ( Harms et al., 2020 Hirsch and Standaert, 2020). However, the relationship between this αSyn deposition, neuronal loss, and other arresting mechanisms during the initiation and progression of PD remains to be undetermined ( Samii et al., 2004). Additionally, the accumulation and spread of alpha-synuclein (αSyn) protein have been suggested as the main disease mechanisms, and its consequent fibrillar intracellular inclusion-Lewy bodies and Lewy neurites-is regarded as the pathologic hallmark of PD ( Nuber et al., 2013 Kouli et al., 2018). Parkinson's disease (PD), which has been considered as the second most common neurodegenerative disease, is characterized by a profound loss of nigrostriatal dopaminergic neurons and its relevant clinical features of Parkinsonism-bradykinesia, rigidity, gait disturbance, and tremor ( Kouli et al., 2018). From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing the PD animal model and monitoring the effect of interventional therapy. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in the PD mouse model. The inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. In analyzing the whole brain, inflammatory responses were activated at the earliest stage, and the soluble αSyn expression increased concurrently. Similar patterns of forefront eruption of inflammation and then followed by αSyn propagation were noted in the opposite striatum, which were not injured by PFF injection. Afterward, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavioral phenotype. In the PFF-injected striatum, inflammatory response cells, including microglia and astrocytes, were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. In this study, with the help of the PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. 5Ilsong Institute of Life Science, Hallym University, Anyang, South KoreaĪccording to a few studies, α-synuclein (αSyn) propagation has been suggested to play a key role in the pathomechanism of Parkinson's disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are not well understood with regard to temporal relationship.4Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea.3Hallym Neurological Institute, Hallym University, Anyang, South Korea.2Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University, Anyang, South Korea.1Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, South Korea.Thuy Thi Lai 1,2,3, Yun Joong Kim 4, Phuong Thi Nguyen 1,5, Young Ho Koh 1,5, Tinh Thi Nguyen 1,5, Hyeo-il Ma 2,3 and Young Eun Kim 2,3 *