Topic: Lewy body diseases

Lewy body diseases (LBD) are complex neurodegenerative conditions that originate from an accumulation of misfolded alpha-synuclein (α-syn) often association with other proteins such as Amyloid β (Aβ), Tau, and TAR-DNA-binding protein. However, the nature of this association is poorly understood. To investigate the complex pathology of LBD, we constructed 2 novel transgenic overexpressing C. elegans models using human genes (α-synA53T;Taupro-agg and α-synA53T;Aβ1-42;Taupro-agg ). We then investigated the molecular, physiologic, and behavioral alterations of these and previously produced models.

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock-down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and