Bibliographic Details
| Title: |
Adaptative Up-Regulation of PRX2 and PRX5 Expression Characterizes Brain from a Mouse Model of Chorea-Acanthocytosis |
| Authors: |
Enrica Federti, Alessandro Matte, Veronica Riccardi, Kevin Peikert, Seth L. Alper, Adrian Danek, Ruth H. Walker, Angela Siciliano, Iana Iatcenko, Andreas Hermann, Lucia De Franceschi |
| Source: |
Antioxidants, Vol 11, Iss 1, p 76 (2021) |
| Publisher Information: |
MDPI AG, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
peroxiredoxin 2, peroxiredoxin 5, neuroinflammation, chorea-acanthocytosis, nilotinib, Lyn, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
The peroxiredoxins (PRXs) constitute a ubiquitous antioxidant. Growing evidence in neurodegenerative disorders such as Parkinson’s disease (PD) or Alzheimer’s disease (AD) has highlighted a crucial role for PRXs against neuro-oxidation. Chorea-acanthocytosis/Vps13A disease (ChAc) is a devastating, life-shortening disorder characterized by acanthocytosis, neurodegeneration and abnormal proteostasis. We recently developed a Vps13a−/− ChAc-mouse model, showing acanthocytosis, neurodegeneration and neuroinflammation which could be restored by LYN inactivation. Here, we show in our Vps13a−/− mice protein oxidation, NRF2 activation and upregulation of downstream cytoprotective systems NQO1, SRXN1 and TRXR in basal ganglia. This was associated with upregulation of PRX2/5 expression compared to wild-type mice. PRX2 expression was age-dependent in both mouse strains, whereas only Vps13a−/− PRX5 expression was increased independent of age. LYN deficiency or nilotinib-mediated LYN inhibition improved autophagy in Vps13a−/− mice. In Vps13a−/−; Lyn−/− basal ganglia, absence of LYN resulted in reduced NRF2 activation and down-regulated expression of PRX2/5, SRXN1 and TRXR. Nilotinib treatment of Vps13a−/− mice reduced basal ganglia oxidation, and plasma PRX5 levels, suggesting plasma PRX5 as a possible ChAc biomarker. Our data support initiation of therapeutic Lyn inhibition as promptly as possible after ChAc diagnosis to minimize development of irreversible neuronal damage during otherwise inevitable ChAc progression. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2076-3921 |
| Relation: |
https://www.mdpi.com/2076-3921/11/1/76; https://doaj.org/toc/2076-3921 |
| DOI: |
10.3390/antiox11010076 |
| Access URL: |
https://doaj.org/article/01dd47480869426cad9fafbd3dbf3ae6 |
| Accession Number: |
edsdoj.01dd47480869426cad9fafbd3dbf3ae6 |
| Database: |
Directory of Open Access Journals |
