Version 1
: Received: 6 March 2024 / Approved: 7 March 2024 / Online: 7 March 2024 (08:06:54 CET)
How to cite:
Zimmer, A.J.; Bahl, C.; Schäfer, J.M.; Weber, J.J.; Riess, O.; Hübener-Schmid, J. p62, the Receptor for Selective Autophagy, Contributes in ATXN3 Aggregate Formation in Spinocerebellar Ataxia Type 3. Preprints2024, 2024030400. https://doi.org/10.20944/preprints202403.0400.v1
Zimmer, A.J.; Bahl, C.; Schäfer, J.M.; Weber, J.J.; Riess, O.; Hübener-Schmid, J. p62, the Receptor for Selective Autophagy, Contributes in ATXN3 Aggregate Formation in Spinocerebellar Ataxia Type 3. Preprints 2024, 2024030400. https://doi.org/10.20944/preprints202403.0400.v1
Zimmer, A.J.; Bahl, C.; Schäfer, J.M.; Weber, J.J.; Riess, O.; Hübener-Schmid, J. p62, the Receptor for Selective Autophagy, Contributes in ATXN3 Aggregate Formation in Spinocerebellar Ataxia Type 3. Preprints2024, 2024030400. https://doi.org/10.20944/preprints202403.0400.v1
APA Style
Zimmer, A.J., Bahl, C., Schäfer, J.M., Weber, J.J., Riess, O., & Hübener-Schmid, J. (2024). p62, the Receptor for Selective Autophagy, Contributes in ATXN3 Aggregate Formation in Spinocerebellar Ataxia Type 3. Preprints. https://doi.org/10.20944/preprints202403.0400.v1
Chicago/Turabian Style
Zimmer, A.J., Olaf Riess and Jeannette Hübener-Schmid. 2024 "p62, the Receptor for Selective Autophagy, Contributes in ATXN3 Aggregate Formation in Spinocerebellar Ataxia Type 3" Preprints. https://doi.org/10.20944/preprints202403.0400.v1
Abstract
Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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