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Underlying Mechanisms of Neuroprotective Actions of Klotho Against Cognitive Impairment in Neurodegenerative Diseases
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Tahereh Ghadiri *   , Maryam Azarfarin , Gholamreza Namvar , Zeynab Samnia |
| Department of Neuroscience and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran , ghadirit@tbzmed.ac.ir |
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Abstract: (109 Views) |
Introduction: Klotho, an elixir of life, beneficially affects several bodily systems, including the brain. During the past two decades, positive effects of klotho in systemic and neurodegenerative diseases have been frequently reported. In this review, we summarized published data addressing these protective effects in neurodegenerative diseases along with associated improvement in cognitive performance. Klotho, a product of the Klotho gene, is a pluripotent protein and exists in soluble, secretary, and transmembrane forms in various types (α, β, and γ). Klotho receptor is localized in several cerebral regions, including the choroid plexus, limbic system, Purkinje cells, hippocampus, and basal ganglia. Klotho has been shown to induce anti-aging effects through the activation of several pathways. Moreover, a growing body of evidence supports its protective and cognition-enhancing effects in different Alzheimer's models. These effects mainly emerged via enhanced synaptic plasticity and clearance of amyloid beta plus improving neuronal energy balance by affecting astrocytes metabolic pathways. Growth factors-related pathways along with Wnt signaling are the most important pathways relating to Klotho functions. Klotho also promotes antioxidant systems, such as superoxide dismutase, to diminish reactive oxygen species and consequently restricts apoptotic cell death. Conclusion: Due to its low regenerative capacity, the brain is of great importance for therapeutic explorations aiming to replace dead neurons. In sum, comprehension of precise mechanism of this protein actions could be promising tool to develop Klotho based-novel therapeutic approaches for treatment of neurodegenerative diseases in the future.
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| Keywords: Alzheimer Disease, Memory, Cognition, Klotho Proteins |
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Full-Text [PDF 987 kb]
(16 Downloads)
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Type of Study: Review --- Open Access, CC-BY-NC |
Subject:
Molecular Neurobiology
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