BACE1 and SCD1 are associated with neurodegeneration

• DOI: 10.3389/fnagi.2023.1194203
• Publication Date: 2023-09-08T15:03:45Z
• Authors: Ferley A. Bedoya-...; Mar Pacheco-Herrero; Ivan Daniel Salom...; Angela Maria Barr...; Johanna Andrea Gu...; Javier Gustavo Vi...; Carlos Andres Vil...; Julián David Aria...; Estela Area-Gomez; Gloria Patricia C...
• Keywords: pro-inflammation; neurodegeneration; PUFAs; Aging Neuroscience; BACE1; Neurosciences. Biological psychiatry. Neuropsychiatry; SCD1; phospholipids; 3. Good health; RC321-571

Introduction Proteolytic processing of amyloid protein precursor by β-site secretase enzyme (BACE1) is dependent on the cellular lipid composition and affected endomembrane trafficking in dementia Alzheimer's disease (AD). Stearoyl-CoA desaturase 1 (SCD1) responsible for synthesis fatty acid monounsaturation (MUFAs), whose accumulation strongly associated with cognitive dysfunction. Methods In this study, we analyzed relationship between BACE1 SCD1 vivo vitro neurodegenerative models their association familial AD (FAD), sporadic (SAD), cerebral autosomal dominant arteriopathy subcortical infarcts leukoencephalopathy (CADASIL) using microscopy, biochemical, mass SPECT approach. Results Our findings showed that immunoreactivities were increased colocalized astrocytes hippocampus a rat model global ischemia (2-VO). A synergistic effect double BACE1/SCD1 silencing recovery motor functions was obtained. This neuroprotective regulation involved segregation phospholipids (PLs) polyunsaturated acids hippocampus, cerebrospinal fluid, serum. The sham ischemic groups stronger serum, inducing an inverse ratio total phosphatydilcholine (PC) lysophosphatidylcholine (LPC), represented mainly reduction PC 38:4 36:4 increase LPC 16:0 18:0. Furthermore, PC:36:4 levels augmented pathological conditions models. increases confirmed FAD, SAD, CADASIL. Conclusion Therefore, suggest novel convergence BACE-1 neurodegeneration, related to pro-inflammatory phospholipids.