Cellular mechanisms of copper neurotoxicity in human, differentiated neurons.

Arch Toxicol

Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Potsdam, Germany.

Published: December 2024

Copper (Cu) is an essential trace element involved in fundamental physiological processes in the human body. Even slight disturbances in the physiological Cu homeostasis are associated with the manifestation of neurodegenerative diseases. While suggesting a crucial role of Cu in the pathogenesis, the exact mechanisms of Cu neurotoxicity involved in the onset and progression of neurological diseases are far from understood. This study focuses on the molecular and cellular mechanisms of Cu-mediated neurotoxicity in human brain cells. First, the cytotoxic potential of Cu was studied in fully differentiated, human neurons (LUHMES cells). Lysosomal integrity was considerably affected following incubation with 420 µM CuSO for 48 h. Further mechanistic studies revealed mitochondria and neuronal network as most susceptible target organelles (already at 100 µM CuSO, 48 h), while the generation of reactive oxygen species turned out to be a rather later consequence of Cu toxicity. Besides Cu, the homeostasis of other elements might be involved and are likely to contribute to the pathology of Cu-mediated neurological disorders. Besides Cu, also effects on the cellular levels of magnesium, calcium, iron, and manganese were observed in the neurons, presumably aggravating the consequences of Cu neurotoxicity. In conclusion, insights in the underlying mode of action will foster the development of treatment strategies against Cu-mediated neurological diseases. Particularly, the interplay of Cu with other elements might provide a powerful diagnostic tool and might be used as therapeutic approach.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-024-03921-0DOI Listing

Publication Analysis

Top Keywords

cellular mechanisms
8
neurotoxicity human
8
neurological diseases
8
cuso 48 h
8
cu-mediated neurological
8
mechanisms copper
4
neurotoxicity
4
copper neurotoxicity
4
human
4
human differentiated
4

Similar Publications

Want 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!