A new zebrafish transgenic line expressing human alpha-synuclein to study the biological basis of Parkinson’s disease

Compelling evidence supports that exploiting both patient-derived and animal models is pivotal to reach a better understanding of Parkinson’s disease (PD) (DOI:10.1002/mds.28387). However, working with in vivo models can be challenging as most of them only partially reproduce the pathology at advanced age.We recently developed a novel zebrafish transgenic (tg) line expressing human full-length alpha-synuclein (aSyn) with an N-terminal mCherry tag named Tg(elavl3:mCherry-hsa.SNCA) which exhibit a series of PD-like features already in the larval stage. At 5 days-post-fertilization (dpf), Tg(elavl3:mCherry-hsa.SNCA embryos showed a significant reduction of tyrosine hydroxylase (TH)-immunopositive neurons and displayed high molecular weight pSer129-aSyn, a marker of mature aggregates, that was absent in controls. Moreover, the Tg(elavl3:mCherry-hsa.SNCA) larvae at 5 dpf exhibited an altered motility response to dark-light conditions, compared to controls. Collectively, these findings supports that Tg(elavl3:mCherry-hsa.SNCA) zebrafish larvae represent a promising complementary model for advanced microscopy studies, including fluorescence lifetime imaging (FLIM), functional assays and super-resolution microscopy to investigate aSyn function and aggregation in the synapse in vivo. Still, this novel zebrafish line appears suitable to test the efficacy of aSyn-targeted therapies by large screening analysis.