Signaling Pathways Involved in Manganese-Induced Neurotoxicity.
Hong ChengBeatriz Ferrer VillahozRomina Deza PonzioMichael AschnerPan ChenPublished in: Cells (2023)
Manganese (Mn) is an essential trace element, but insufficient or excessive bodily amounts can induce neurotoxicity. Mn can directly increase neuronal insulin and activate insulin-like growth factor (IGF) receptors. As an important cofactor, Mn regulates signaling pathways involved in various enzymes. The IGF signaling pathway plays a protective role in the neurotoxicity of Mn, reducing apoptosis in neurons and motor deficits by regulating its downstream protein kinase B (Akt), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR). In recent years, some new mechanisms related to neuroinflammation have been shown to also play an important role in Mn-induced neurotoxicity. For example, DNA-sensing receptor cyclic GMP-AMP synthase (cCAS) and its downstream signal efficient interferon gene stimulator (STING), NOD-like receptor family pyrin domain containing 3(NLRP3)-pro-caspase1, cleaves to the active form capase1 (CASP1), nuclear factor κB (NF-κB), sirtuin (SIRT), and Janus kinase (JAK) and signal transducers and activators of the transcription (STAT) signaling pathway. Moreover, autophagy, as an important downstream protein degradation pathway, determines the fate of neurons and is regulated by these upstream signals. Interestingly, the role of autophagy in Mn-induced neurotoxicity is bidirectional. This review summarizes the molecular signaling pathways of Mn-induced neurotoxicity, providing insight for further understanding of the mechanisms of Mn.
Keyphrases
- signaling pathway
- pi k akt
- induced apoptosis
- protein kinase
- high glucose
- room temperature
- oxidative stress
- diabetic rats
- epithelial mesenchymal transition
- nuclear factor
- cell cycle arrest
- transition metal
- cell proliferation
- cell death
- metal organic framework
- drug induced
- traumatic brain injury
- endothelial cells
- endoplasmic reticulum stress
- type diabetes
- dna methylation
- binding protein
- toll like receptor
- ischemia reperfusion injury
- body mass index
- gene expression
- brain injury
- spinal cord injury
- pseudomonas aeruginosa
- lipopolysaccharide induced
- cerebral ischemia
- skeletal muscle
- immune response
- circulating tumor cells