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Folic acid and S-adenosylmethionine reverse Homocysteine-induced Alzheimer's disease-like pathological changes in rat hippocampus by modulating PS1 and PP2A methylation levels.
Sun, Shoudan; Lu, Wei; Zhang, Chunhong; Wang, Guanyu; Hou, Yue; Zhou, Jian; Wang, Yonghui.
Afiliación
  • Sun S; Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250031, China.
  • Lu W; Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250031, China.
  • Zhang C; Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250031, China.
  • Wang G; Institute of Environmental and Operational Medicine, Tianjin 30050, China.
  • Hou Y; Institute of Environmental and Operational Medicine, Tianjin 30050, China.
  • Zhou J; School of Public Health, Weifang Medical College, Weifang 261053, China. Electronic address: wfyxyzhou@163.com.
  • Wang Y; Institute of Environmental and Operational Medicine, Tianjin 30050, China. Electronic address: wyhui77@sohu.com.
Brain Res ; 1841: 149095, 2024 Oct 15.
Article en En | MEDLINE | ID: mdl-38917878
ABSTRACT

BACKGROUND:

Abnormally elevated homocysteine (Hcy) is recognized as a biomarker and risk factor for Alzheimer's disease (AD). However, the underlying mechanisms by which Hcy affects AD are still unclear.

OBJECTIVES:

This study aimed to elucidate the effects and mechanisms by which Hcy affects AD-like pathological changes in the hippocampus through in vivo and in vitro experiments, and to investigate whether folic acid (FA) and S-adenosylmethionine (SAM) supplementation could improve neurodegenerative injuries.

METHODS:

In vitro experiments hippocampal neurons of rat were treated with Hcy, FA or SAM for 24 h; while the hyperhomocysteinemia (HHcy) in Wistar rats was established by intraperitoneal injection of Hcy, and FA was added to feed. The expression of ß-amyloid (Aß), phosphorylated tau protein, presenilin 1 (PS1) at the protein level and the activity of protein phosphatase 2A (PP2A) were detected, the immunopositive cells for Aß and phosphorylated tau protein in the rat hippocampus were also evaluated by immunohistochemical staining.

RESULTS:

FA and SAM significantly repressed Hcy-induced AD-like pathological changes in the hippocampus, including the increased tau protein phosphorylation at Ser214, Ser396 and the expression of Aß42. In addition, Hcy-induced PS1 expression increased at the protein level and PP2A activity decreased, while FA and SAM were able to retard that.

CONCLUSIONS:

The increase in PS1 expression and decrease in PP2A activity may be the mechanisms underlying the Hcy-induced AD-like pathology. FA and SAM significantly repressed the Hcy-induced neurodegenerative injury by modulating PS1 and PP2A methylation levels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Péptidos beta-Amiloides / Proteínas tau / Ratas Wistar / Presenilina-1 / Proteína Fosfatasa 2 / Enfermedad de Alzheimer / Ácido Fólico / Hipocampo / Homocisteína Límite: Animals Idioma: En Revista: Brain Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Péptidos beta-Amiloides / Proteínas tau / Ratas Wistar / Presenilina-1 / Proteína Fosfatasa 2 / Enfermedad de Alzheimer / Ácido Fólico / Hipocampo / Homocisteína Límite: Animals Idioma: En Revista: Brain Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos