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S-Adenosylmethionine Rescues Cognitive Deficits in the rTg4510 Animal Model by Stabilizing Protein Phosphatase 2A and Reducing Phosphorylated Tau.
Beauchamp, Leah C; Liu, Xiang M; Sedjahtera, Amelia; Bogeski, Mirjana; Vella, Laura J; Bush, Ashley I; Adlard, Paul A; Barnham, Kevin J.
Afiliación
  • Beauchamp LC; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
  • Liu XM; Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Australia.
  • Sedjahtera A; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
  • Bogeski M; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
  • Vella LJ; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
  • Bush AI; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
  • Adlard PA; Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia.
  • Barnham KJ; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
J Alzheimers Dis ; 77(4): 1705-1715, 2020.
Article en En | MEDLINE | ID: mdl-32925070
BACKGROUND: Alterations in the methionine cycle and abnormal tau phosphorylation are implicated in many neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia. rTg4510 mice express mutant human P301L tau and are a model of tau hyperphosphorylation. The cognitive deficit seen in these animals correlates with a burden of hyperphosphorylated tau and is a model to test therapies aimed at lowering phosphorylated tau. OBJECTIVE: This study aimed to increase protein phosphatase 2A activity through supplementation of S-adenosylmethionine and analyze the effect on spatial memory and tau in treated animals. METHODS: 6-month-old rTg4510 mice were treated with 100 mg/kg S-adenosylmethionine by oral gavage for 3 weeks. Spatial recognition memory was tested in the Y-maze. Alterations to phosphorylated tau and protein phosphatase 2A were explored using immunohistochemistry, western blot, and enzyme-linked immunosorbent assays. RESULTS: Treatment with S-adenosylmethionine increased the Y-maze novel arm exploration time and increased both the expression and activity of protein phosphatase 2A. Furthermore, treatment reduced the number of AT8 positive neurons and reduced the expression of phosphorylated tau (Ser202/Thr205). S-adenosylmethionine contributes to multiple pathways in neuronal homeostasis and neurodegeneration. CONCLUSION: This study shows that supplementation with S-adenosylmethionine stabilizes the heterotrimeric form of PP2A resulting in an increase the enzymatic activity, a reduced level of pathological tau, and improved cognition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Proteínas tau / Proteína Fosfatasa 2 / Disfunción Cognitiva Límite: Animals Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Proteínas tau / Proteína Fosfatasa 2 / Disfunción Cognitiva Límite: Animals Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Países Bajos