Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology
Parkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in the pentose phosphate pathway and purine metabolism. Cortical hubs, which...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1507033/full |
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| author | Hirohisa Watanabe Sayuri Shima Kazuya Kawabata Yasuaki Mizutani Akihiro Ueda Akihiro Ueda Mizuki Ito Mizuki Ito |
| author_facet | Hirohisa Watanabe Sayuri Shima Kazuya Kawabata Yasuaki Mizutani Akihiro Ueda Akihiro Ueda Mizuki Ito Mizuki Ito |
| author_sort | Hirohisa Watanabe |
| collection | DOAJ |
| description | Parkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in the pentose phosphate pathway and purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple brain functions, require significant energy due to their dense synaptic activity and long-range connections. Deficits in ATP production in PD can severely impair these hubs. The energy imbalance also affects subcortical regions, including the massive axonal arbors in the striatum of substantia nigra pars compacta neurons, due to their high metabolic demand. This ATP decline may result in α-synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown and accelerated neurodegeneration. We propose an “ATP Supply–Demand Mismatch Model” to help explain the pathogenesis of PD. This model emphasizes how ATP deficits drive pathological protein aggregation, impaired autophagy, and the degeneration of key brain networks, contributing to both motor and non-motor symptoms. |
| format | Article |
| id | doaj-art-9f6753c05cdf4da19f8cd194a8f8da70 |
| institution | Kabale University |
| issn | 1662-5099 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj-art-9f6753c05cdf4da19f8cd194a8f8da702025-01-22T07:11:31ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-01-011710.3389/fnmol.2024.15070331507033Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathologyHirohisa Watanabe0Sayuri Shima1Kazuya Kawabata2Yasuaki Mizutani3Akihiro Ueda4Akihiro Ueda5Mizuki Ito6Mizuki Ito7Department of Neurology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, Fujita Health University Okazaki Medical Center, Okazaki, JapanDepartment of Neurology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, Fujita Health University Bantane Hospital, Nagoya, JapanParkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in the pentose phosphate pathway and purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple brain functions, require significant energy due to their dense synaptic activity and long-range connections. Deficits in ATP production in PD can severely impair these hubs. The energy imbalance also affects subcortical regions, including the massive axonal arbors in the striatum of substantia nigra pars compacta neurons, due to their high metabolic demand. This ATP decline may result in α-synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown and accelerated neurodegeneration. We propose an “ATP Supply–Demand Mismatch Model” to help explain the pathogenesis of PD. This model emphasizes how ATP deficits drive pathological protein aggregation, impaired autophagy, and the degeneration of key brain networks, contributing to both motor and non-motor symptoms.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1507033/fullATP metabolismcortical hubsmitochondrial dysfunctionα-synuclein aggregationenergy imbalancehypoxanthine |
| spellingShingle | Hirohisa Watanabe Sayuri Shima Kazuya Kawabata Yasuaki Mizutani Akihiro Ueda Akihiro Ueda Mizuki Ito Mizuki Ito Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology Frontiers in Molecular Neuroscience ATP metabolism cortical hubs mitochondrial dysfunction α-synuclein aggregation energy imbalance hypoxanthine |
| title | Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology |
| title_full | Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology |
| title_fullStr | Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology |
| title_full_unstemmed | Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology |
| title_short | Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology |
| title_sort | brain network and energy imbalance in parkinson s disease linking atp reduction and α synuclein pathology |
| topic | ATP metabolism cortical hubs mitochondrial dysfunction α-synuclein aggregation energy imbalance hypoxanthine |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1507033/full |
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