Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy
Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to e...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/5/641 |
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| author | Federica Scalia Everly Conway de Macario Giuseppe Bonaventura Francesco Cappello Alberto J. L. Macario |
| author_facet | Federica Scalia Everly Conway de Macario Giuseppe Bonaventura Francesco Cappello Alberto J. L. Macario |
| author_sort | Federica Scalia |
| collection | DOAJ |
| description | Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools. |
| first_indexed | 2024-03-11T03:55:24Z |
| format | Article |
| id | doaj.art-1ca4a0982f5c47229e61efc5a8e6a408 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T03:55:24Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-1ca4a0982f5c47229e61efc5a8e6a4082023-11-18T00:32:20ZengMDPI AGBiology2079-77372023-04-0112564110.3390/biology12050641Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized TherapyFederica Scalia0Everly Conway de Macario1Giuseppe Bonaventura2Francesco Cappello3Alberto J. L. Macario4Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo (UNIPA), 90127 Palermo, ItalyEuro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo (UNIPA), 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo (UNIPA), 90127 Palermo, ItalyEuro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, ItalyGenetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools.https://www.mdpi.com/2079-7737/12/5/641chaperone systemmolecular chaperonechaperonopathiesdistal neuropathieshuman CCTCCT5 mutation |
| spellingShingle | Federica Scalia Everly Conway de Macario Giuseppe Bonaventura Francesco Cappello Alberto J. L. Macario Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy Biology chaperone system molecular chaperone chaperonopathies distal neuropathies human CCT CCT5 mutation |
| title | Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy |
| title_full | Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy |
| title_fullStr | Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy |
| title_full_unstemmed | Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy |
| title_short | Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy |
| title_sort | histopathology of skeletal muscle in a distal motor neuropathy associated with a mutant cct5 subunit clues for future developments to improve differential diagnosis and personalized therapy |
| topic | chaperone system molecular chaperone chaperonopathies distal neuropathies human CCT CCT5 mutation |
| url | https://www.mdpi.com/2079-7737/12/5/641 |
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