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Secreted and Transmembrane αKlotho Isoforms Have Different Spatio-Temporal Profiles in the Brain during Aging and Alzheimer's Disease Progression
Massó Chacón, Anna (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Sánchez, Angela (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Giménez Llort, Lydia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Lizcano de Vega, José Miguel (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Cañete Ríos, Manuel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
García, Belen (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Torres-Lista, Virginia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Puig, Meritxell (Universitat Autònoma de Barcelona. Centre de Biotecnologia Animal i Teràpia Gènica (CBATEG))
Bosch i Merino, Assumpció (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Chillón Rodríguez, Miguel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date: 2015
Abstract: The Klotho protein is a β-glucuronidase, and its overexpression is associated with life extension. Its mechanism of action is not fully understood, although it has been recently reported that αKlotho improves synaptic and cognitive functions, and it may also influence a variety of structures and functions during CNS maturation and aging. The αKlotho gene has two transcripts, one encoding a transmembrane isoform (m-KL), and the other a putative secreted isoform (s-KL). Unfortunately, little is known about the secreted αKlotho isoform, since available antibodies cannot discriminate s-KL from the KL1 domain cleaved from the transmembrane isoform. This study shows, for the first time, that the klotho transcript produced by alternative splicing generates a stable protein (70 kDa), and that in contrast to the transmembrane Klotho isoform, it is ten times more abundant in the brain than in the kidney suggesting that the two isoforms may have different functions. We also studied whether klotho expression in the CNS was influenced by aging, Alzheimer's disease (AD), or a healthy lifestyle, such as voluntary moderate continuous exercise. We observed a strong correlation between high expression levels of the two klotho transcripts and the healthy status of the animals. Expression of Klotho in brain areas decayed more rapidly in the 3xTg-AD model of AD than in healthy animals, whilst moderate continuous exercise in adulthood prevents the decline in expression of both klotho transcripts.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Alzheimer disease ; Hippocampus ; Aging ; Cerebellum ; Kidneys ; Prefrontal cortex ; Central nervous system ; Alternative splicing
Published in: PLoS one, Vol. 10, Num. 11 (November 2015) , p. 1-15, ISSN 1932-6203

DOI: 10.1371/journal.pone.0143623
PMID: 26599613


15 p, 1.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2017-02-28, last modified 2018-07-28



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