Cadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading to AB and phosphorylated Tau protein generation and cell death

Moyano-Cires Ivanoff, Paula VivianaGarcía Sánchez, José ManuelLobo Alonso, MargaritaAnadón Baselga, María JoséSola Vendrell, EmmaPelayo Alarcón, AdelaGarcía Lobo, JimenaFrejo Moya, María TeresaPino Sans, Javier Del2024-02-082024-02-082018-09-11Cadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading to AB and phosphorylated Tau protein generation and cell death. Paula Moyano, Jose Manuel García, Margarita Lobo, María José Anadon, Emma Sola, Adela Pelayo, Jimena García, Maria Teresa Frejo, Javier del Pino. Food and Chemical Toxicology 121 (2018): 297-3080278-691510.1016/j.fct.2018.09.016https://hdl.handle.net/20.500.14352/100512Cadmium, a neurotoxic environmental compound, produces cognitive disorders, although the mechanism remains unknown. Cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF), mediated, in part, by increase in Aβ and total and phosphorylated Tau protein levels, which may explain cadmium effects on learning and memory processes. Cadmium downregulates the expression of heat shock proteins (HSPs) HSP 90, HSP70 and HSP27, and of HSF1, the master regulator of the HSP pathway. HSPs proteins reduce the production of Aβ and phosphorylated Tau proteins and avoid cell death pathways induction. Thus, we hypothesized that cadmium induced the production of Aβ and Tau proteins by HSP pathway disruption through HSF1 expression alteration, leading to BF cholinergic neurons cell death. Our results show that cadmium downregulates HSF1, leading to HSP90, HSP70 and HSP27 gene expression downregulation in BF SN56 cholinergic neurons. In addition, cadmium induced Aβ and total and phosphorylated Tau proteins generation, mediated partially by HSP90, HSP70 and HSP27 disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons.engAttribution-NonCommercial-NoDerivatives 4.0 InternationalCadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading to AB and phosphorylated Tau protein generation and cell deathjournal article1873-6351https://www.sciencedirect.com/science/article/pii/S0278691518306604?via=ihub30213552https://pubmed.ncbi.nlm.nih.gov/30213552/restricted accessCadmium neurotoxicityCognitive disordersHSF1Heat shock proteinsSN56 basal forebrain cholinergic neuronsToxicología (Medicina)Neurociencias (Medicina)3214 Toxicología3205.07 Neurología