Identification of Clec7a as the therapeutic target of rTMS in alleviating Parkinson's disease: targeting neuroinflammation

Chen, Xueyun; Feng, Sining; Yin, Bo; Zhou, Yi; Ba, Fang

doi:10.1016/j.bbadis.2023.166814

Cited by 8 publications

(3 citation statements)

References 64 publications

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“…Genetic and pharmacological targeting of Dectin-1 modifies many different neurological conditions, including AD 9,18,22 , MS 17 , PD 23 , stroke 24,25 , optic nerve injury [19][20][21] , and axonal injury 34 . Several of these studies have used a Dectin-1 knockout model, which harbours a deletion of exons 1-3, corresponding to the cytoplasmic tail, transmembrane region, and stalk 31 .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study showed that knockout of Dectin-1 ameliorated cognitive deficits and neurodegeneration in AD mice 22 . Similarly, adeno-associated virus-mediated knockdown of Dectin-1 alleviated motor deficits and neurodegeneration in a Parkinson's disease (PD) rat model 23 . Furthermore, pharmacological inhibition of Dectin-1 partially rescued the disease phenotypes in mouse models of ischemic stroke 24 and intracerebral hemorrhage 25 .…”

Section: Introductionmentioning

confidence: 99%

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Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

You,

Maksimovic,

Chen

et al. 2024

Preprint

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Microglia have been increasingly implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Dectin-1, encoded by the Clec7a gene, is highly upregulated in a specific microglial response state called disease-associated microglia (DAM) in various neurodegenerative conditions. However, the role of Dectin-1 in ALS is undetermined. Here, we show that Clec7a mRNA upregulation occurs in central nervous system (CNS) regions that exhibit neurodegeneration in a MATR3 S85C knock-in mouse model (Matr3S85C/S85C) of ALS. Furthermore, a significant increase in the number of Dectin-1+ microglia coincides with the onset of motor deficits, and this number increases with disease severity. We demonstrate that the knockout of Dectin-1 does not affect survival, motor function, neurodegeneration, or microglial responses in Matr3S85C/S85C mice. These findings suggest that Dectin-1 does not play a role in modifying ALS onset or progression but could potentially serve as a valuable biomarker for ALS severity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

You,

Maksimovic,

Chen

et al. 2024

Preprint

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show abstract

“…While one limitation of analyzing tissue in bulk is that it does not allow us to assign the changes in gene expression to certain cell types, it is an interesting notion that some of the most significantly changed genes in PFF-injected mice, e.g., Cst7, Itgax, Clec7a, and Lilrb4, are found to be expressed by disease-associated microglia in models of Alzheimer's disease [51][52][53], suggesting that shared microglial responses exist between protein-misfolding diseases. Additionally, the upregulation of Clec7a, encoding the pathogen recognition receptor Clec7a, in microglia has recently been shown to promote neuroinflammation in a mouse model of Parkinson's disease [54], while the roles of Cst7, Itgax, and Lilrb4 in relation to Parkinson's disease remain to be further investigated. Furthermore, we found that Tnf was differentially expressed upon PFF treatment, consistent with published in vitro data from primary microglia [28].…”

Section: Discussionmentioning

confidence: 99%

Characterization of pSer129-αSyn Pathology and Neurofilament Light-Chain Release across In Vivo, Ex Vivo, and In Vitro Models of Pre-Formed-Fibril-Induced αSyn Aggregation

Hansen,

Ambjørn,

Harndahl

et al. 2024

Cells

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Protein aggregation is a predominant feature of many neurodegenerative diseases, including synucleinopathies, which are characterized by cellular inclusions containing α-Synuclein (αSyn) phosphorylated at serine 129 (pSer129). In the present study, we characterized the development of αSyn pre-formed fibril (PFF)-induced pSer129-αSyn pathology in F28tg mice overexpressing human wild-type αSyn, as well as in ex vivo organotypic cultures and in vitro primary cultures from the same mouse model. Concurrently, we collected cerebrospinal fluid (CSF) from mice and conditioned media from ex vivo and in vitro cultures and quantified the levels of neurofilament light chain (NFL), a biomarker of neurodegeneration. We found that the intra-striatal injection of PFFs induces the progressive spread of pSer129-αSyn pathology and microglial activation in vivo, as well as modest increases in NFL levels in the CSF. Similarly, PFF-induced αSyn pathology occurs progressively in ex vivo organotypic slice cultures and is accompanied by significant increases in NFL release into the media. Using in vitro primary hippocampal cultures, we further confirmed that pSer129-αSyn pathology and NFL release occur in a manner that correlates with the fibril dose and the level of the αSyn protein. Overall, we demonstrate that αSyn pathology is associated with NFL release across preclinical models of seeded αSyn aggregation and that the pharmacological inhibition of αSyn aggregation in vitro also significantly reduces NFL release.

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Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

You,

Maksimovic,

Metri

et al. 2024

Heliyon

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Identification of Clec7a as the therapeutic target of rTMS in alleviating Parkinson's disease: targeting neuroinflammation

Cited by 8 publications

References 64 publications

Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

Characterization of pSer129-αSyn Pathology and Neurofilament Light-Chain Release across In Vivo, Ex Vivo, and In Vitro Models of Pre-Formed-Fibril-Induced αSyn Aggregation

Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

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