Nrf2 is an antioxidant transcriptional activator in many types of cells, and its dysfunction plays key roles in a variety of human disorders, including Parkinson's disease (PD). PD is characterized by the selective loss of dopaminergic neurons in PD-affected brain regions. Dopamine treatment of neuronal cells stimulates the production of reactive oxygen species (ROS) and increases ROS-dependent neuronal apoptosis. In this study, we found that the ubiquitin-specific protease 10 (USP10) protein reduces dopamine-induced ROS production of neuronal cells and ROS-dependent apoptosis by stimulating the antioxidant activity of Nrf2. USP10 interacted with the Nrf2 activator p62, increased the phosphorylation of p62, increased the interaction of p62 with the Nrf2 inhibitor Keap1, and stimulated Nrf2 antioxidant transcriptional activity. In addition, USP10 augmented dopamine-induced Nrf2 translation. Taken together, these results indicate that USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells and suggest that USP10 activators are promising therapeutic agents for oxidative stress-related diseases, including PD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689211 | PMC |
| http://dx.doi.org/10.1016/j.jbc.2021.101448 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gain-of-function ANXA11 mutation cause late-onset ALS with aberrant protein aggregation, neuroinflammation and autophagy impairment.
Acta Neuropathol Commun
January 2025
Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College (PUMC) and Chinese Academy of Medical Science (CAMS), Beijing, China.
Mutations in the ANXA11 gene, encoding an RNA-binding protein, have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but the underlying in vivo mechanisms remain unclear. This study examines the clinical features of ALS patients harboring the ANXA11 hotspot mutation p.P36R, characterized by late-onset motor neuron disease and occasional multi-system involvement.
View Article and Find Full Text PDFDelivery of Prime editing in human stem cells using pseudoviral NanoScribes particles.
Nat Commun
January 2025
CIRI, Centre International de Recherche en Infectiologie Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.
Prime Editing can rewrite genes in living cells by allowing point mutations, deletions, or insertion of small DNA sequences with high precision. However, its safe and efficient delivery into human stem cells remains a technical challenge. In this report, we engineer Nanoscribes, virus-like particles that encapsidate ribonucleoprotein complexes of the Prime Editing system and allow their delivery into recipient cells.
View Article and Find Full Text PDFRoles for Prlhr/GPR10 and Npffr2/GPR74 in Feeding Responses to PrRP.
Mol Metab
January 2025
Department of Internal Medicine, University of Michigan, Ann Arbor, MI USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. Electronic address:
Several groups of neurons in the NTS suppress food intake, including Prlh-expressing neurons (NTS cells). Not only does the artificial activation of NTS cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We used animals lacking PrRP receptors GPR10 and/or GRP74 (encoded by Prlhr and Npffr2, respectively) to determine roles for each in the restraint of food intake and body weight by the increased expression of Prlh in NTS neurons (NTS mice) and in response to the anorectic PrRP analog, p52.
View Article and Find Full Text PDFOctadecaneuropeptide promotes the migration of astrocyte via ODN metabotropic receptor and calcium signaling pathway.
Peptides
January 2025
University of Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecules Valorisation. 2092 Tunis, Tunisia.
Migration is an essential characteristic of cells that occurs during many physiological and pathological processes. Astrocytes represent the most abundant cell type in the adult central nervous system (CNS), that play a crucial role in various functions such as guiding and supporting neuronal migration during development and maintaining brain homeostasis at adulthood. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN).
View Article and Find Full Text PDFLong-range directional growth of neurites induced by magnetic forces.
Acta Biomater
January 2025
School of Life Sciences, Keele University, Staffordshire, UK. Electronic address:
The ability to control the growth and orientation of neurites over long distances has significant implications for regenerative therapies and the development of physiologically relevant brain tissue models. In this study, the forces generated on magnetic nanoparticles internalised within intracellular endosomes are used to direct the orientation of neuronal outgrowth in cell cultures. Following differentiation, neurite orientation was observed after 3 days application of magnetic forces to human neuroblastoma (SH-SY5Y) cells, and after 4 days application to rat cortical primary neurons.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!