Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity
<p dir="ltr">Klotho, a well-known aging suppressor protein, has been implicated in neuroprotection and the regulation of neuronal senescence. While previous studies have demonstrated its anti-aging properties in human brain organoids, its potential to mitigate neurodegenerative proce...
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| مؤلفون آخرون: | , , , |
| منشور في: |
2025
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| _version_ | 1864513534654676992 |
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| author | Mohammed R. Shaker (10316180) |
| author2 | Salam Salloum-Asfar (656363) Rowaida Z. Taha (8854754) Ibrahim Javed (3478850) Ernst J. Wolvetang (10316186) |
| author2_role | author author author author |
| author_facet | Mohammed R. Shaker (10316180) Salam Salloum-Asfar (656363) Rowaida Z. Taha (8854754) Ibrahim Javed (3478850) Ernst J. Wolvetang (10316186) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mohammed R. Shaker (10316180) Salam Salloum-Asfar (656363) Rowaida Z. Taha (8854754) Ibrahim Javed (3478850) Ernst J. Wolvetang (10316186) |
| dc.date.none.fl_str_mv | 2025-03-28T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s13041-025-01199-6 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Klotho_overexpression_protects_human_cortical_neurons_from_-amyloid_induced_neuronal_toxicity/30405286 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Neurosciences Klotho β-amyloid Neurodegeneration iPSCs Cortical neurons Alzheimer’s disease Neuroprotection |
| dc.title.none.fl_str_mv | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Klotho, a well-known aging suppressor protein, has been implicated in neuroprotection and the regulation of neuronal senescence. While previous studies have demonstrated its anti-aging properties in human brain organoids, its potential to mitigate neurodegenerative processes triggered by β-amyloid remains underexplored. In this study, we utilised human induced pluripotent stem cells (iPSCs) engineered with a doxycycline-inducible system to overexpress <i>KLOTHO</i> and generated 2D cortical neuron cultures from these cells. These neurons were next exposed to pre-aggregated β-amyloid 1–42 oligomers to model the neurotoxicity associated with Alzheimer’s disease. Our data reveal that upregulation of <i>KLOTHO</i> significantly reduced β-amyloid-induced neuronal degeneration and apoptosis, as evidenced by decreased cleaved caspase-3 expression and preservation of axonal integrity. Additionally, <i>KLOTHO</i> overexpression prevented the loss of dendritic branching and mitigated reductions in axonal diameter, hallmark features of neurodegenerative pathology. These results highlight Klotho’s protective role against β-amyloid-induced neurotoxicity in human cortical neurons and suggest that its age-related decline may contribute to neurodegenerative diseases such as Alzheimer’s disease. Our findings underscore the therapeutic potential of Klotho-based interventions in mitigating age-associated neurodegenerative processes.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Brain<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13041-025-01199-6" target="_blank">https://dx.doi.org/10.1186/s13041-025-01199-6</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_9c18d316657fdc1f4368d9ae0b0c388c |
| identifier_str_mv | 10.1186/s13041-025-01199-6 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30405286 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicityMohammed R. Shaker (10316180)Salam Salloum-Asfar (656363)Rowaida Z. Taha (8854754)Ibrahim Javed (3478850)Ernst J. Wolvetang (10316186)Biomedical and clinical sciencesNeurosciencesKlothoβ-amyloidNeurodegenerationiPSCsCortical neuronsAlzheimer’s diseaseNeuroprotection<p dir="ltr">Klotho, a well-known aging suppressor protein, has been implicated in neuroprotection and the regulation of neuronal senescence. While previous studies have demonstrated its anti-aging properties in human brain organoids, its potential to mitigate neurodegenerative processes triggered by β-amyloid remains underexplored. In this study, we utilised human induced pluripotent stem cells (iPSCs) engineered with a doxycycline-inducible system to overexpress <i>KLOTHO</i> and generated 2D cortical neuron cultures from these cells. These neurons were next exposed to pre-aggregated β-amyloid 1–42 oligomers to model the neurotoxicity associated with Alzheimer’s disease. Our data reveal that upregulation of <i>KLOTHO</i> significantly reduced β-amyloid-induced neuronal degeneration and apoptosis, as evidenced by decreased cleaved caspase-3 expression and preservation of axonal integrity. Additionally, <i>KLOTHO</i> overexpression prevented the loss of dendritic branching and mitigated reductions in axonal diameter, hallmark features of neurodegenerative pathology. These results highlight Klotho’s protective role against β-amyloid-induced neurotoxicity in human cortical neurons and suggest that its age-related decline may contribute to neurodegenerative diseases such as Alzheimer’s disease. Our findings underscore the therapeutic potential of Klotho-based interventions in mitigating age-associated neurodegenerative processes.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Brain<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13041-025-01199-6" target="_blank">https://dx.doi.org/10.1186/s13041-025-01199-6</a></p>2025-03-28T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s13041-025-01199-6https://figshare.com/articles/journal_contribution/Klotho_overexpression_protects_human_cortical_neurons_from_-amyloid_induced_neuronal_toxicity/30405286CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/304052862025-03-28T09:00:00Z |
| spellingShingle | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity Mohammed R. Shaker (10316180) Biomedical and clinical sciences Neurosciences Klotho β-amyloid Neurodegeneration iPSCs Cortical neurons Alzheimer’s disease Neuroprotection |
| status_str | publishedVersion |
| title | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| title_full | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| title_fullStr | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| title_full_unstemmed | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| title_short | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| title_sort | Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity |
| topic | Biomedical and clinical sciences Neurosciences Klotho β-amyloid Neurodegeneration iPSCs Cortical neurons Alzheimer’s disease Neuroprotection |