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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Shukla AK,Spurrier J,Kuzina I,Giniger Edoi
10.1016/j.celrep.2018.12.025subject
Has Abstractpub_date
2019-01-02 00:00:00pages
131-144.e4issue
1issn
2211-1247pii
S2211-1247(18)31955-7journal_volume
26pub_type
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