Long Noncoding RNA NR_030777 Alleviates Cobalt Nanoparticles-Induced Neurodegenerative Damage by Promoting...

Area of Science:

• Environmental Health
• Neuroscience
• Toxicology

Background:

• Cobalt nanoparticles (CoNPs) are increasingly prevalent in industrial and medical applications.
• Growing evidence links CoNP exposure to neurotoxicity, but mechanisms remain unclear.
• A systematic assessment of CoNP-induced central nervous system (CNS) impairment is needed.

Purpose of the Study:

• To investigate the neurodegenerative effects of CoNPs in vivo and in vitro.
• To elucidate the molecular mechanisms underlying CoNP-induced neurotoxicity, focusing on autophagy.
• To explore the potential protective role of long noncoding RNA NR_030777.

Main Methods:

• In vivo and in vitro models were used to assess CoNP exposure effects.
• Autophagosome formation, lysosomal fusion, and TFEB levels were analyzed.
• NR_030777 expression and its interaction with TFEB mRNA were investigated.

Main Results:

• CoNPs induced neurodegeneration, cognitive impairment, β-amyloid deposition, and Tau hyperphosphorylation.
• CoNPs disrupted autophagic flux by impeding autophagosomal-lysosomal fusion and reducing TFEB levels.
• Overexpression of NR_030777 mitigated CoNP-induced neurotoxicity by stabilizing TFEB mRNA.

Conclusions:

• Autophagic dysfunction is a key mechanism in CoNP-induced neurodegeneration.
• NR_030777 plays a protective role against CoNP neurotoxicity by restoring autophagic-lysosomal function.
• This study proposes an adverse outcome pathway for CoNP CNS toxicity assessment.