Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease
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Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease. / Ferreira, Sara A.; Li, Conghui; Klæstrup, Ida H.; Vitic, Zagorka; Rasmussen, Rikke K.; Kirkegaard, Asger; Toft, Gitte U.; Betzer, Cristine; Svendsen, Pia; Jensen, Poul H.; Luo, Yonglun; Etzerodt, Anders; Moestrup, Søren K.; Romero-Ramos, Marina.
In: npj Parkinson's Disease, Vol. 9, No. 1, 164, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson’s disease
AU - Ferreira, Sara A.
AU - Li, Conghui
AU - Klæstrup, Ida H.
AU - Vitic, Zagorka
AU - Rasmussen, Rikke K.
AU - Kirkegaard, Asger
AU - Toft, Gitte U.
AU - Betzer, Cristine
AU - Svendsen, Pia
AU - Jensen, Poul H.
AU - Luo, Yonglun
AU - Etzerodt, Anders
AU - Moestrup, Søren K.
AU - Romero-Ramos, Marina
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson’s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.
AB - Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson’s disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.
U2 - 10.1038/s41531-023-00606-w
DO - 10.1038/s41531-023-00606-w
M3 - Journal article
C2 - 38092806
AN - SCOPUS:85179888209
VL - 9
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
SN - 2373-8057
IS - 1
M1 - 164
ER -
ID: 377801998