Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia in older people. AD is associated with the loss of synapses, oxidative stress, mitochondrial structural and functional abnormalities, microRNA deregulation, inflammatory responses, neuronal...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6098 |
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| author | Ashly Hindle Sharda P. Singh Jangampalli Adi Pradeepkiran Chhanda Bose Murali Vijayan Sudhir Kshirsagar Neha A. Sawant P. Hemachandra Reddy |
| author_facet | Ashly Hindle Sharda P. Singh Jangampalli Adi Pradeepkiran Chhanda Bose Murali Vijayan Sudhir Kshirsagar Neha A. Sawant P. Hemachandra Reddy |
| author_sort | Ashly Hindle |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia in older people. AD is associated with the loss of synapses, oxidative stress, mitochondrial structural and functional abnormalities, microRNA deregulation, inflammatory responses, neuronal loss, accumulation of amyloid-beta (Aβ) and phosphorylated tau (p-tau). AD occurs in two forms: early onset, familial AD and late-onset, sporadic AD. Causal factors are still unknown for a vast majority of AD patients. Genetic polymorphisms are proposed to contribute to late-onset AD via age-dependent increases in oxidative stress and mitochondrial abnormalities. Recent research from our lab revealed that reduced levels of Rlip76 induce oxidative stress, mitochondrial dysfunction and synaptic damage, leading to molecular and behavioral phenotypes resembling late-onset AD. Rlip76 is a multifunctional 76 kDa protein encoded by the <i>RALBP1</i> gene, located on chromosome 18. Rlip is a stress-protective ATPase of the mercapturic acid pathway that couples clathrin-dependent endocytosis with the efflux of glutathione–electrophile conjugates. Rlip is evolutionarily highly conserved across species and is ubiquitously expressed in all tissues, including AD-affected brain regions, the cerebral cortex and hippocampus, where highly active neuronal metabolisms render the cells highly susceptible to intracellular oxidative damage. In the current article, we summarize molecular and cellular features of Rlip and how depleted Rlip may exacerbate oxidative stress, mitochondrial dysfunction and synaptic damage in AD. We also discuss the possible role of Rlip in aspects of learning and memory via axonal growth, dendritic remodeling, and receptor regulation. We conclude with a discussion of the potential for the contribution of genetic polymorphisms in Rlip to AD progression and the potential for Rlip-based therapies. |
| first_indexed | 2024-03-10T01:15:53Z |
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| language | English |
| last_indexed | 2024-03-10T01:15:53Z |
| publishDate | 2022-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-250b4f9e9f6f4d00bab0b23663b674202023-11-23T14:09:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311609810.3390/ijms23116098Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?Ashly Hindle0Sharda P. Singh1Jangampalli Adi Pradeepkiran2Chhanda Bose3Murali Vijayan4Sudhir Kshirsagar5Neha A. Sawant6P. Hemachandra Reddy7Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USAAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia in older people. AD is associated with the loss of synapses, oxidative stress, mitochondrial structural and functional abnormalities, microRNA deregulation, inflammatory responses, neuronal loss, accumulation of amyloid-beta (Aβ) and phosphorylated tau (p-tau). AD occurs in two forms: early onset, familial AD and late-onset, sporadic AD. Causal factors are still unknown for a vast majority of AD patients. Genetic polymorphisms are proposed to contribute to late-onset AD via age-dependent increases in oxidative stress and mitochondrial abnormalities. Recent research from our lab revealed that reduced levels of Rlip76 induce oxidative stress, mitochondrial dysfunction and synaptic damage, leading to molecular and behavioral phenotypes resembling late-onset AD. Rlip76 is a multifunctional 76 kDa protein encoded by the <i>RALBP1</i> gene, located on chromosome 18. Rlip is a stress-protective ATPase of the mercapturic acid pathway that couples clathrin-dependent endocytosis with the efflux of glutathione–electrophile conjugates. Rlip is evolutionarily highly conserved across species and is ubiquitously expressed in all tissues, including AD-affected brain regions, the cerebral cortex and hippocampus, where highly active neuronal metabolisms render the cells highly susceptible to intracellular oxidative damage. In the current article, we summarize molecular and cellular features of Rlip and how depleted Rlip may exacerbate oxidative stress, mitochondrial dysfunction and synaptic damage in AD. We also discuss the possible role of Rlip in aspects of learning and memory via axonal growth, dendritic remodeling, and receptor regulation. We conclude with a discussion of the potential for the contribution of genetic polymorphisms in Rlip to AD progression and the potential for Rlip-based therapies.https://www.mdpi.com/1422-0067/23/11/6098RALBP1RlipneurodegenerationAlzheimer’s diseaseoxidative stressmitochondrial dysfunction |
| spellingShingle | Ashly Hindle Sharda P. Singh Jangampalli Adi Pradeepkiran Chhanda Bose Murali Vijayan Sudhir Kshirsagar Neha A. Sawant P. Hemachandra Reddy Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? International Journal of Molecular Sciences RALBP1 Rlip neurodegeneration Alzheimer’s disease oxidative stress mitochondrial dysfunction |
| title | Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? |
| title_full | Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? |
| title_fullStr | Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? |
| title_full_unstemmed | Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? |
| title_short | Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? |
| title_sort | rlip76 an unexplored player in neurodegeneration and alzheimer s disease |
| topic | RALBP1 Rlip neurodegeneration Alzheimer’s disease oxidative stress mitochondrial dysfunction |
| url | https://www.mdpi.com/1422-0067/23/11/6098 |
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