Drosophila Spaghetti and Doubletime Link the Circadian Clock and Light to Caspases, Apoptosis and Tauopathy

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Alzheimer’s disease is the most common cause of dementia in the aging population. It is a progressive neurodegenerative disorder that attacks the brain neurons, resulting in loss of memory, thinking and behavioral changes. One pathological hallmark is aggregation of the microtubule-associated protein Tau. A growing body of evidence highlights the importance of caspase-dependent Tau truncation in initiation and potentiation of Tau aggregation. Here we use the fruit fly Drosophila to examine the links between circadian rhythms, aging, apoptosis and Alzheimer’s Disease. We identified a regulator (spag) of the circadian kinase Dbt that functions to stabilize Dbt during the middle of the day. In addition, the caspase Dronc is regulated by Dbt and Spag and, when activated by reduction of either, targets Tau for cleavage, leading to behavioral deficits and shortened lifespans. The expression of activated caspase occurs in several parts of the brain in a manner requiring signaling from a neuropeptide produced by circadian cells. Wild type flies with no genetic modifications eventually exhibit modified Dbt and expression of activated caspase at specific times of day, further demonstrating the links between the circadian clock, light and apoptosis.

Vyšlo v časopise: Drosophila Spaghetti and Doubletime Link the Circadian Clock and Light to Caspases, Apoptosis and Tauopathy. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005171
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005171

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