Zscan21, or zinc finger and SCAN domain containing 21, is a transcription factor. It is involved in the transcriptional regulation of SNCA, the gene encoding α -synuclein, which is strongly implicated in Parkinson disease (PD) [1,2,4,5,6]. Zscan21 may also be associated with Alzheimer's disease as its expression was found to be related to obesity metrics in a study on AD-related genes [3].

In PD research, Zscan21 has complex effects on SNCA transcription. Lentivirus-mediated silencing of Zscan21 in primary neuronal cultures led to variable results: it increased SNCA promoter activity, mRNA, and protein levels in cortical cultures but reduced SNCA in neurosphere cultures [2]. In vivo, efficient adeno-associated virus-mediated knockdown of Zscan21 in the postnatal and adult hippocampus did not significantly alter SNCA levels, suggesting possible compensatory mechanisms [2]. Additionally, rare genetic variants in Zscan21 occur in patients with familial forms of PD, and expression of these variants results in the stabilization of the Zscan21 protein [1].

In conclusion, Zscan21 plays a role in the transcriptional regulation of SNCA, which is relevant to PD pathogenesis. Studies using knockdown models in neuronal cultures and in vivo have provided insights into its complex regulatory effects on SNCA expression. However, its exact role in vivo may be influenced by compensatory mechanisms. Understanding Zscan21 could potentially offer new perspectives for PD research and treatment [1,2].