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Sequestosome-1 (SQSTM1/p62) as a target in dopamine catabolite-mediated cellular dyshomeostasis

Pubblicato il: 25.06.2024 17:06

Sequestosome-1 (SQSTM1/p62) as a target in dopamine catabolite-mediated cellular dyshomeostasis.

Alterations in the dopamine catabolic pathway are known to contribute to the degeneration of nigrostriatal neurons in Parkinson’s disease (PD). The progressive cellular buildup of the highly reactive intermediate 3,4-dihydroxyphenylacetaldehye (DOPAL) generates protein cross-linking, oligomerization of the PD-linked αSynuclein and imbalance in protein quality control. In the work published in Cell Death and Disease (https://www.nature.com/articles/s41419-024-06763-x) coordinated by Dr Anna Masato (PhD at DiBio UNIPD, currently a post-doc at University College London, UK) and Prof Luigi Bubacco (DiBio UNIPD), the autophagic cargo sequestome-1 (SQSTM1/p62) emerges as a target of DOPAL-dependent oligomerization. The substantial impact on p62 proteostasis caused by DOPAL appears of relevance for dopaminergic neurodegeneration, in which the progressive failure of degradative pathways and the deposition of proteins like αSynuclein, ubiquitin and p62 in inclusion bodies represent a major trait of PD pathology. In addition, these findings provide further insight on p62 pathophysiology, which has been linked to several neurodegenerative diseases given its central role in regulating protein quality control.

 




Ultimo aggiornamento: 25.06.2024 17:24