TY - JOUR
T1 - Role of Astrocytes in Parkinson’s Disease Associated with Genetic Mutations and Neurotoxicants
AU - Kim, Sanghoon
AU - Pajarillo, Edward
AU - Nyarko-Danquah, Ivan
AU - Aschner, Michael
AU - Lee, Eunsook
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia, resulting in movement impairment referred to as parkinsonism. However, the etiology of PD is not well known, with genetic factors accounting only for 10–15% of all PD cases. The pathogenetic mechanism of PD is not completely understood, although several mechanisms, such as oxidative stress and inflammation, have been suggested. Understanding the mechanisms of PD pathogenesis is critical for developing highly efficacious therapeutics. In the PD brain, dopaminergic neurons degenerate mainly in the basal ganglia, but recently emerging evidence has shown that astrocytes also significantly contribute to dopaminergic neuronal death. In this review, we discuss the role of astrocytes in PD pathogenesis due to mutations in α-synuclein (PARK1), DJ-1 (PARK7), parkin (PARK2), leucine-rich repeat kinase 2 (LRRK2, PARK8), and PTEN-induced kinase 1 (PINK1, PARK6). We also discuss PD experimental models using neurotoxins, such as paraquat, rotenone, 6-hydroxydopamine, and MPTP/MPP+. A more precise and comprehensive understanding of astrocytes’ modulatory roles in dopaminergic neurodegeneration in PD will help develop novel strategies for effective PD therapeutics.
AB - Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia, resulting in movement impairment referred to as parkinsonism. However, the etiology of PD is not well known, with genetic factors accounting only for 10–15% of all PD cases. The pathogenetic mechanism of PD is not completely understood, although several mechanisms, such as oxidative stress and inflammation, have been suggested. Understanding the mechanisms of PD pathogenesis is critical for developing highly efficacious therapeutics. In the PD brain, dopaminergic neurons degenerate mainly in the basal ganglia, but recently emerging evidence has shown that astrocytes also significantly contribute to dopaminergic neuronal death. In this review, we discuss the role of astrocytes in PD pathogenesis due to mutations in α-synuclein (PARK1), DJ-1 (PARK7), parkin (PARK2), leucine-rich repeat kinase 2 (LRRK2, PARK8), and PTEN-induced kinase 1 (PINK1, PARK6). We also discuss PD experimental models using neurotoxins, such as paraquat, rotenone, 6-hydroxydopamine, and MPTP/MPP+. A more precise and comprehensive understanding of astrocytes’ modulatory roles in dopaminergic neurodegeneration in PD will help develop novel strategies for effective PD therapeutics.
KW - 6-hydroxydopamine
KW - DJ-1
KW - LRRK2
KW - MPTP
KW - Parkinson’s disease
KW - astrocytes
KW - paraquat
KW - parkin
KW - rotenone
KW - α-synuclein
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U2 - 10.3390/cells12040622
DO - 10.3390/cells12040622
M3 - Review article
C2 - 36831289
AN - SCOPUS:85148731431
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 4
M1 - 622
ER -