Identification of ADP/ATP Translocase 1 as a Novel Glycoprotein and Its Association with Parkinson’s Disease

Zhang, Wenli; Li, Jun; Chen, Qianhui; Ding, Wenyong; Li, Sheng; Ma, Li

doi:10.1007/s11064-022-03688-9

Cited by 2 publications

(2 citation statements)

References 26 publications

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Section: Astrocytic Ripk3 Signaling Promotes Neurodegeneration In The...mentioning

confidence: 99%

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Chang,

DaPrano,

Lindman

et al. 2024

JCI Insight

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Astrocyte activation is a common feature of neurodegenerative diseases. However, the ways in which dying neurons influence the activity of astrocytes is poorly understood. Receptor interacting protein kinase-3 (RIPK3) signaling has recently been described as a key regulator of neuroinflammation, but whether this kinase mediates astrocytic responsiveness to neuronal death has not yet been studied.Here, we used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease to show that activation of astrocytic RIPK3 drives dopaminergic cell death and axon damage.Transcriptomic profiling revealed that astrocytic RIPK3 promoted gene expression associated with neuroinflammation and movement disorders, and this coincided with significant engagement of damage associated molecular pattern (DAMP) signaling. In mechanistic experiments, we show that factors released from dying neurons signal through receptor for advanced glycation endproducts (RAGE) to induce astrocytic RIPK3 signaling, which conferred inflammatory and neurotoxic functional activity.These findings highlight a mechanism of neuron-glia crosstalk in which neuronal death perpetuates further neurodegeneration by engaging inflammatory astrocyte activation via RIPK3.

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Section: Astrocytic Ripk3 Signaling Promotes Neurodegeneration In The...mentioning

confidence: 99%

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Chang,

DaPrano,

Lindman

et al. 2024

JCI Insight

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show abstract

“…This phenotype was also greatly ameliorated in Ripk3 fl/fl Aldh1l1 Cre+ mice. To test whether these differences in dopaminergic neuron loss were associated with differences in motor function, we next subjected mice to the vertical grid maze, a motor task previously shown to be sensitive to perturbations of dopaminergic circuits 34,35 . Strikingly, MPTP-treated control mice exhibited significantly impaired performance in the vertical grid maze (Figure 1F-G), while mice lacking astrocytic Ripk3 did not.…”

Section: Astrocytic Ripk3 Signaling Promotes Pathogenesis In the Mptp...mentioning

confidence: 99%

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Chang,

DaPrano,

Evans

et al. 2023

Preprint

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Astrocyte activation is a common feature of neurodegenerative diseases. However, the ways in which dying neurons influence the activity of astrocytes is poorly understood. RIPK3 signaling has recently been described as a key regulator of neuroinflammation, but whether this kinase mediates astrocytic responsiveness to neuronal death has not yet been studied. Here, we used the MPTP model of Parkinson′s disease to show that activation of astrocytic RIPK3 drives dopaminergic cell death and axon damage. Transcriptomic profiling revealed that astrocytic RIPK3 promoted gene expression associated with neuroinflammation and movement disorders, and this coincided with significant engagement of DAMP signaling. Using human cell culture systems, we show that factors released from dying neurons signal through RAGE to induce RIPK3-dependent astrocyte activation. These findings highlight a mechanism of neuron-glia crosstalk in which neuronal death perpetuates further neurodegeneration by engaging inflammatory astrocyte activation via RIPK3.

show abstract

Identification of ADP/ATP Translocase 1 as a Novel Glycoprotein and Its Association with Parkinson’s Disease

Cited by 2 publications

References 26 publications

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

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