Overexpression of cellular stress proteins in skin fibroblast with presenilin 1 mutation.

• DOI: 10.1002/alz.053170
• Publication Date: 2021-12-01
• Authors: Gustavo Lopez‐Toledo; Maria‐del‐Carmen ...; José Antonio Aria...; María del Carmen ...
• Keywords: Hyperphosphorylation

The accumulation and aggregation of misfolded proteins in the human brain are known to be an essential feature many neurodegenerative diseases, presenilin-1 (PS1) mutations linked Alzheimer's disease (AD) have been suggested alter protein response (UPR) due stress on endoplasmic reticulum. Moreover, deal with generated by aggregation, cells use a series protection mechanisms. One these biological responses involves called molecular chaperones that mediate folding, signaling, surveillance, cell protection. These changes cellular not only seen neurons brains from AD patients but also peripheral disease, emphasizing systemic nature this pathology. Besides, difficulties studying dynamic processes brain, valuable for diagnosis understanding mechanisms AD.We cultured fibroblasts affected familial presenilin 1 mutation (M146L or A246E) control subjects, Minimum Essential Medium Eagle 15% non-inactivated fetal bovine serum. were characterized immunodetection karyotyping. Pathways related neurodegeneration analyzed western blot. Finally, we carried out proteomic study using mass spectrometry fibroblast´s profile controls.We identified differences expression autophagic-lysosomal pathway individual´s fibroblasts. We kinases hyperphosphorylation tau protein. derived groups (HSPA8, HSP90AB1, HSPD1, HSPE1) present controls. From Western blot analysis, confirmed overexpression HSP90, HSP70, HSP60.In summary, our results indicate FAD-PS1 show altered pathways associated stress, autophagy, lysosomes, phosphorylation protein, which shows can useful search modeling neurodegeneration, as well identification early biomarkers AD.