Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice
| Autor: | Kaitlyn Ho, Gui Qiu Yu, Lennart Mucke, Carmela R. Abraham, Lei Zhu, Pascal E. Sanchez, Erik C. B. Johnson, Makoto Kuro-o, Alexander Betourne, Lauren Broestl, Daniel Kim, Dena B. Dubal, Kurtresha Worden, Eliezer Masliah |
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| Rok vydání: | 2015 |
| Předmět: |
cognition
Aging klotho Hippocampus Neurodegenerative urologic and male genital diseases Alzheimer's Disease Medical and Health Sciences Transgenic Mice Amyloid beta-Protein Precursor Cognition Receptors Amyloid precursor protein 2.1 Biological and endogenous factors Aetiology Klotho Glucuronidase Behavior Animal biology General Neuroscience Long-term potentiation Articles female genital diseases and pregnancy complications Mental Health Neurological NMDA receptor Alzheimer's disease Psychology N-Methyl-D-Aspartate Genetically modified mouse medicine.medical_specialty mice Longevity Mice Transgenic tau Proteins Receptors N-Methyl-D-Aspartate NMDA receptors Basic Behavioral and Social Science Internal medicine Behavioral and Social Science medicine Acquired Cognitive Impairment Genetics Animals Humans Maze Learning Klotho Proteins Behavior Neurology & Neurosurgery Animal Prevention Psychology and Cognitive Sciences Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) medicine.disease Brain Disorders Endocrinology Good Health and Well Being Synaptic plasticity Synapses biology.protein Dementia Nerve Net Cognition Disorders Neuroscience |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 35, iss 6 |
| Popis: | Aging is the principal demographic risk factor for Alzheimer disease (AD), the most common neurodegenerative disorder. Klotho is a key modulator of the aging process and, when overexpressed, extends mammalian lifespan, increases synaptic plasticity, and enhances cognition. Whether klotho can counteract deficits related to neurodegenerative diseases, such as AD, is unknown. Here we show that elevating klotho expression decreases premature mortality and network dysfunction in human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Increasing klotho levels prevented depletion of NMDA receptor (NMDAR) subunits in the hippocampus and enhanced spatial learning and memory in hAPP mice. Klotho elevation in hAPP mice increased the abundance of the GluN2B subunit of NMDAR in postsynaptic densities and NMDAR-dependent long-term potentiation, which is critical for learning and memory. Thus, increasing wild-type klotho levels or activities improves synaptic and cognitive functions, and may be of therapeutic benefit in AD and other cognitive disorders. |
| Databáze: | OpenAIRE |
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