One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases
Abstract Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been fo...
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BMC
2025-06-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02277-x |
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| author | Marta Cozzi Barbara Tedesco Veronica Ferrari Marta Chierichetti Paola Pramaggiore Laura Cornaggia Rocio Magdalena Maria Brodnanova Ali Mohamed Carmelo Milioto Margherita Piccolella Mariarita Galbiati Paola Rusmini Valeria Crippa Cinzia Gellera Stefania Magri Franco Taroni Riccardo Cristofani Angelo Poletti |
| author_facet | Marta Cozzi Barbara Tedesco Veronica Ferrari Marta Chierichetti Paola Pramaggiore Laura Cornaggia Rocio Magdalena Maria Brodnanova Ali Mohamed Carmelo Milioto Margherita Piccolella Mariarita Galbiati Paola Rusmini Valeria Crippa Cinzia Gellera Stefania Magri Franco Taroni Riccardo Cristofani Angelo Poletti |
| author_sort | Marta Cozzi |
| collection | DOAJ |
| description | Abstract Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been found in the KIF5A gene and a link between the specific domain in the encoded protein affected by mutations and the associated phenotype has become evident. Point mutations targeting KIF5A motor and stalk domains, that are expected to impair KIF5A motility, mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease. Oppositely, translational frameshifts causing the elongation of KIF5A tail enhance KIF5A migration towards cell periphery, induce kinesin aggregation, and are linked to amyotrophic lateral sclerosis (ALS) or neonatal intractable myoclonus (NEIMY). This review correlates KIF5A structure and roles in neuronal trafficking with its involvement in the above-mentioned neurodegenerative and neurodevelopmental conditions. |
| format | Article |
| id | doaj-art-afc58b8a0f124bbd8d7d5f81396208d1 |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-afc58b8a0f124bbd8d7d5f81396208d12025-08-20T03:22:53ZengBMCCell Communication and Signaling1478-811X2025-06-0123111310.1186/s12964-025-02277-xOne gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseasesMarta Cozzi0Barbara Tedesco1Veronica Ferrari2Marta Chierichetti3Paola Pramaggiore4Laura Cornaggia5Rocio Magdalena6Maria Brodnanova7Ali Mohamed8Carmelo Milioto9Margherita Piccolella10Mariarita Galbiati11Paola Rusmini12Valeria Crippa13Cinzia Gellera14Stefania Magri15Franco Taroni16Riccardo Cristofani17Angelo Poletti18Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” (DiSFeB), University of MilanAbstract Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been found in the KIF5A gene and a link between the specific domain in the encoded protein affected by mutations and the associated phenotype has become evident. Point mutations targeting KIF5A motor and stalk domains, that are expected to impair KIF5A motility, mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease. Oppositely, translational frameshifts causing the elongation of KIF5A tail enhance KIF5A migration towards cell periphery, induce kinesin aggregation, and are linked to amyotrophic lateral sclerosis (ALS) or neonatal intractable myoclonus (NEIMY). This review correlates KIF5A structure and roles in neuronal trafficking with its involvement in the above-mentioned neurodegenerative and neurodevelopmental conditions.https://doi.org/10.1186/s12964-025-02277-xKIF5AHereditary spastic paraplegiaCharcot-Marie-Tooth diseaseAmyotrophic lateral sclerosisNeonatal intractable myoclonus |
| spellingShingle | Marta Cozzi Barbara Tedesco Veronica Ferrari Marta Chierichetti Paola Pramaggiore Laura Cornaggia Rocio Magdalena Maria Brodnanova Ali Mohamed Carmelo Milioto Margherita Piccolella Mariarita Galbiati Paola Rusmini Valeria Crippa Cinzia Gellera Stefania Magri Franco Taroni Riccardo Cristofani Angelo Poletti One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases Cell Communication and Signaling KIF5A Hereditary spastic paraplegia Charcot-Marie-Tooth disease Amyotrophic lateral sclerosis Neonatal intractable myoclonus |
| title | One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases |
| title_full | One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases |
| title_fullStr | One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases |
| title_full_unstemmed | One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases |
| title_short | One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases |
| title_sort | one gene many phenotypes the role of kif5a in neurodegenerative and neurodevelopmental diseases |
| topic | KIF5A Hereditary spastic paraplegia Charcot-Marie-Tooth disease Amyotrophic lateral sclerosis Neonatal intractable myoclonus |
| url | https://doi.org/10.1186/s12964-025-02277-x |
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