ArticleCell reports2019
Hyperactive Innate Immunity Causes Degeneration of Dopamine Neurons upon Altering Activity of Cdk5.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
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- Emerging roles of antimicrobial peptides in innate immunity, neuronal function, and neurodegeneration.Trends in neurosciences · 2024Review
- Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation.PLoS genetics · 2024Article
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Manipulating mitochondrial reactive oxygen species alters survival in unexpected ways in a Drosophila Cdk5 model of neurodegeneration.Biology open · 2024Article
- Changes in mitochondrial distribution occur at the axon initial segment in association with neurodegeneration in Drosophila.Biology open · 2024Article
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- The Drosophila ZNRF1/2 homologue, detour, interacts with HOPS complex and regulates autophagy.Communications biology · 2024Article
- Changes in mitochondrial distribution occur at the axon initial segment in association with neurodegeneration inbioRxiv : the preprint server for biology · 2024Article
- Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation.bioRxiv : the preprint server for biology · 2023Article
- Mutations in abnormal spindle disrupt temporal transcription factor expression and trigger immune responses in the Drosophila brain.Genetics · 2023Article
- Article
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Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. Here, we identify a molecular pathway that links innate immunity to age-dependent loss of dopaminergic neurons in Drosophila. We find, first, that altering the expression of the activating subunit of the Cdk5 protein kinase (Cdk5α) causes severe disruption of autophagy. Second, this disruption of autophagy is both necessary and sufficient to cause the hyperactivation of innate immunity, particularly expression of anti-microbial peptides. Finally, it is the upregulation of immunity that induces the age-dependent death of dopaminergic neurons. Given the dysregulation of Cdk5 and innate immunity in human neurodegeneration and the conserved role of the kinase in the regulation of autophagy, this sequence is likely to have direct application to the chain of events in human neurodegenerative disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.