Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity
Leukodystrophies represent a heterogeneous group of disorders characterized by specific genetic mutations, metabolic abnormalities, and degeneration of white matter in the central nervous system. These disorders are classified into several categories, with X-linked adrenoleukodystrophy (X-ALD), meta...
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2024-11-01
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| author | Dar-Shong Lin Che-Sheng Ho |
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| description | Leukodystrophies represent a heterogeneous group of disorders characterized by specific genetic mutations, metabolic abnormalities, and degeneration of white matter in the central nervous system. These disorders are classified into several categories, with X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD), and globoid cell leukodystrophy (GLD) being the most prevalent demyelinating leukodystrophies in pediatric populations. Maintaining proteostasis, which is critical for normal cellular function, relies fundamentally on the ubiquitin–proteasome system (UPS) and autophagy for the degradation of misfolded and damaged proteins. Compelling evidence has highlighted the critical roles of UPS and autophagy dysfunction in the pathogenesis of neurodegenerative diseases. Given the complex and poorly understood pathomechanisms underlying demyelinating leukodystrophies, coupled with the pressing need for effective therapeutic strategies, this review aims to systemically analyze the molecular and pathological evidence linking UPS and autophagy dysfunction to demyelinating leukodystrophies, specifically X-ALD and GLD. Furthermore, we will assess the therapeutic potential of autophagy modulators in the management of X-ALD and GLD, with the objective to inspire further research into therapeutic approaches that target autophagy and UPS pathways. Novel therapies that enhance autophagy and UPS function hold promise as complementary regimens in combination therapies aimed at achieving comprehensive correction of the pathogenic mechanisms in demyelinating leukodystrophies. |
| format | Article |
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| language | English |
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| spelling | doaj-art-5c389ffbc60a4a2c8eed22743af0f8572025-08-20T01:53:44ZengMDPI AGCells2073-44092024-11-011322187310.3390/cells13221873Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic OpportunityDar-Shong Lin0Che-Sheng Ho1Department of Translational Medicine, MacKay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei 10449, TaiwanDepartment of Neurology, MacKay Children’s Hospital, Taipei 10449, TaiwanLeukodystrophies represent a heterogeneous group of disorders characterized by specific genetic mutations, metabolic abnormalities, and degeneration of white matter in the central nervous system. These disorders are classified into several categories, with X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD), and globoid cell leukodystrophy (GLD) being the most prevalent demyelinating leukodystrophies in pediatric populations. Maintaining proteostasis, which is critical for normal cellular function, relies fundamentally on the ubiquitin–proteasome system (UPS) and autophagy for the degradation of misfolded and damaged proteins. Compelling evidence has highlighted the critical roles of UPS and autophagy dysfunction in the pathogenesis of neurodegenerative diseases. Given the complex and poorly understood pathomechanisms underlying demyelinating leukodystrophies, coupled with the pressing need for effective therapeutic strategies, this review aims to systemically analyze the molecular and pathological evidence linking UPS and autophagy dysfunction to demyelinating leukodystrophies, specifically X-ALD and GLD. Furthermore, we will assess the therapeutic potential of autophagy modulators in the management of X-ALD and GLD, with the objective to inspire further research into therapeutic approaches that target autophagy and UPS pathways. Novel therapies that enhance autophagy and UPS function hold promise as complementary regimens in combination therapies aimed at achieving comprehensive correction of the pathogenic mechanisms in demyelinating leukodystrophies.https://www.mdpi.com/2073-4409/13/22/1873white matter diseasesdemyelinating leukodystrophiesX-linked adrenoleukodystrophygloboid cell leukodystrophyautophagyubiquitin–proteasome system |
| spellingShingle | Dar-Shong Lin Che-Sheng Ho Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity Cells white matter diseases demyelinating leukodystrophies X-linked adrenoleukodystrophy globoid cell leukodystrophy autophagy ubiquitin–proteasome system |
| title | Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity |
| title_full | Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity |
| title_fullStr | Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity |
| title_full_unstemmed | Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity |
| title_short | Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity |
| title_sort | emerging role of ubiquitin proteasome system and autophagy in pediatric demyelinating leukodystrophies and therapeutic opportunity |
| topic | white matter diseases demyelinating leukodystrophies X-linked adrenoleukodystrophy globoid cell leukodystrophy autophagy ubiquitin–proteasome system |
| url | https://www.mdpi.com/2073-4409/13/22/1873 |
| work_keys_str_mv | AT darshonglin emergingroleofubiquitinproteasomesystemandautophagyinpediatricdemyelinatingleukodystrophiesandtherapeuticopportunity AT cheshengho emergingroleofubiquitinproteasomesystemandautophagyinpediatricdemyelinatingleukodystrophiesandtherapeuticopportunity |