Age- and α-Synuclein-Dependent Degeneration of Dopamine and Noradrenaline Neurons in the Annual Killifish Nothobranchius furzeri

Abstract

Highlights d Annual killifish reveals age-dependent degeneration of dopamine neurons d Aged Nothobranchius furzeri shows accumulation of a-synuclein in the brain d Dopamine neurodegeneration is ameliorated by genetic depletion of a-synuclein

LRRK2 Kinase Inhibition Rescues Deficits in Lysosome Function Due to Heterozygous GBA1 Expression in Human iPSC-Derived Neurons

“…Next, we sought to determine the levels of oligomeric species of secreted αSyn by using an antibody that specifically recognizes αSyn oligomers. To test the specificity of this antibody, we conducted a dot blot with purified αSyn monomer and pre-formed fibrils and observed that the antibody is unable to detect monomeric αSyn while it robustly recognized fibrillar αSyn, consistent with prior efforts validating this reagent (Lassen et al, 2018;Krashia et al, 2019;Matsui et al, 2019). Finally, we analyzed the conditioned media from WT and GBA1 heterozygous-null iNs and found that secreted αSyn from GBA1 heterozygous-null iNs contain more oligomeric αSyn than that from WT cells ( Figure 3D).…”

Mosaic Heterochrony in Neural Progenitors Sustains Accelerated Brain Growth and Neurogenesis in the Juvenile Killifish N. furzeri

“…The killifish is a newly co-opted vertebrate model for aging studies, because of its exceptionally short lifespan [25,26]. Recent studies are beginning to explore causal factors of its accelerated aging, including in the brain [27][28][29][30][31]. The fast aging in N. furzeri is hypothesized by some authors to be a trade-off to rapid larval and juvenile growth, but this lead remains mechanistically unexplored [32].…”

Mosaic heterochrony in neural progenitors sustains accelerated brain growth and neurogenesis in the juvenile killifish N. furzeri

“…The killifish is a newly co-opted vertebrate model for aging studies, due to its exceptionally short lifespan (Cellerino et al, 2016;. Recent studies are beginning to explore causal factors of its accelerated aging, including in the brain Cui et al, 2019;Tozzini et al, 2012;Ripa et al, 2017;Matsui et al, 2019). The fast ageing in N.furzeri is hypothesized by some authors to be a trade-off to rapid larval and juvenile growth, but this lead remains mechanistically unexplored (Reichard and Polačik, 2019).…”