Manganese increases Aβ and Tau protein levels through proteasome 20S and heat shock proteins 90 and 70 alteration, leading to SN56 cholinergic cell death following single and repeated treatment

Moyano-Cires Ivanoff, Paula VivianaGarcía Sánchez, José ManuelGarcía Lobo, JimenaAnadón Baselga, María JoséNaval López, María VictoriaFrejo Moya, María TeresaSola Vendrell, EmmaPelayo Alarcón, AdelaPino Sans, Javier Del2024-02-082024-02-082020Manganese increases Aβ and Tau protein levels through proteasome 20S and heat shock proteins 90 and 70 alteration, leading to SN56 cholinergic cell death following single and repeated treatment. Moyano P, García JM, García J, Anadon MJ, Naval MV, Frejo MT, Sola E, Pelayo A, Pino JD. Ecotoxicology and Environmental Safety. 2020 Oct 15:203:1109750147-651310.1016/j.ecoenv.2020.110975https://hdl.handle.net/20.500.14352/100524Manganese (Mn) produces cholinergic neuronal loss in basal forebrain (BF) region that was related to cognitive dysfunction induced after single and repeated Mn treatment. All processes that generate cholinergic neuronal loss in BF remain to be understood. Mn exposure may produce the reduction of BF cholinergic neurons by increasing amyloid beta (Aβ) and phosphorylated Tau (pTau) protein levels, altering heat shock proteins’ (HSPs) expression, disrupting proteasome P20S activity and generating oxidative stress. These mechanisms, described to be altered by Mn in regions different than BF, could lead to the memory and learning process alteration produced after Mn exposure. The research performed shows that single and repeated Mn treatment of SN56 cholinergic neurons from BF induces P20S inhibition, increases Aβ and pTau protein levels, produces HSP90 and HSP70 proteins expression alteration, and oxidative stress generation, being the last two effects mediated by NRF2 pathway alteration. The increment of Aβ and pTau protein levels was mediated by HSPs and proteasome dysfunction. All these mechanisms mediated the cell decline observed after Mn treatment. Our results are relevant because they may assist to reveal the processes leading to the neurotoxicity and cognitive alterations observed after Mn exposure.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Manganese increases Aβ and Tau protein levels through proteasome 20S and heat shock proteins 90 and 70 alteration, leading to SN56 cholinergic cell death following single and repeated treatmentjournal articlehttps://www.doi.org/10.1016/j.ecoenv.2020.11097532678756open access61SN56 basal forebrain cholinergic neuronsManganeseHeat shock proteinsAβ and pTau proteinsToxicología (Medicina)Neurociencias (Medicina)3214 Toxicología3205.07 Neurología