BACE1 and SCD1 are associated with neurodegeneration

Frontiers in Aging Neuroscience

Aging Neuroscience

Estela Area-Gomez¹  Julián David Arias-Londoño²  Ferley A. Bedoya-Guzmán³  Ivan Daniel Salomon-Cruz³  Gloria Patricia Cardona Gomez³  Carlos Andres Villegas Lanau³  Angela Maria Barrera-Sandoval³  Javier Gustavo Villamil-Ortiz³  Johanna Andrea Gutierrez Vargas⁴  Mar Pacheco-Herrero⁵ 

[1] Department of Neurology, Columbia University Medical Center, New York, NY, United States;Department of Systems Engineering, University of Antioquia UdeA, Medellín, Colombia;Faculty of Medicine University of Antioquia, Cellular and Molecular Neurobiology Area and Neurobank, Group of Neuroscience (GNA), Medellín, Colombia;Faculty of Medicine University of Antioquia, Cellular and Molecular Neurobiology Area and Neurobank, Group of Neuroscience (GNA), Medellín, Colombia;Grupo de Investigación en Salud del Adulto Mayor (GISAM), Corporación Universitaria Remington, Medellín, Colombia;Faculty of Medicine University of Antioquia, Cellular and Molecular Neurobiology Area and Neurobank, Group of Neuroscience (GNA), Medellín, Colombia;Neuroscience Research Laboratory, Faculty of Health Sciences, Pontificia Universidad Católica Madre y Maestra, Santiago de los Caballeros, Dominican Republic;

关键词: BACE1;    SCD1;    neurodegeneration;    phospholipids;    PUFAs;    pro-inflammation;   

DOI  :  10.3389/fnagi.2023.1194203

 received in 2023-04-26, accepted in 2023-08-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

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

【 授权许可】

Unknown   
Copyright © 2023 Bedoya-Guzmán, Pacheco-Herrero, Salomon-Cruz, Barrera-Sandoval, Gutierrez Vargas, Villamil-Ortiz, Villegas Lanau, Arias-Londoño, Area-Gomez and Cardona Gomez.