The <i>shaggy</i> Gene Encoding the GSK3 Protein Kinase Controls the Sex-Dependent Effects of Specific Clusters of D. <i>melanogaster</i> Dopaminergic Neurons on Lifespan

Dopaminergic neurons control behavior, memory, and locomotion, and the causal relationship of their dysfunction to neurodegenerative diseases and aging has drawn attention to investigating the involvement of dopaminergic neurons in the regulation of lifespan. The highly conserved serine-threonine protein kinase GSK3 (Glycogen Syntase Kinase 3), one of the most important multifunctional cellular enzymes in higher organisms, which in Drosophila melanogaster is encoded by the shaggy gene, plays an important role in the function of dopaminergic neurons. This paper provides the first evidence that altering shaggy expression levels in just a few clusters of dopaminergic neurons can affect lifespan. This effect can be either negative or positive and depends on sex. The data obtained may serve as a basis for further search for targeted cell-specific factors regulating the rate of aging, as well as for the development of highly specific approaches to the therapy of neurodegenerative diseases.