Exploring the zinc-related transcriptional landscape in Alzheimer’s disease
Alzheimer’s disease (AD) is a progressive neurological disorder, and increasing evidence suggests AD pathology is driven by metabolic dysfunction in the brain. Zinc is the second most abundant trace element found in the human body and is required by all living organisms. Zinc is used extensively in...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | IBRO Neuroscience Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242122000410 |
| _version_ | 1828266786070462464 |
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| author | Daniel C. Shippy Tyler K. Ulland |
| author_facet | Daniel C. Shippy Tyler K. Ulland |
| author_sort | Daniel C. Shippy |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a progressive neurological disorder, and increasing evidence suggests AD pathology is driven by metabolic dysfunction in the brain. Zinc is the second most abundant trace element found in the human body and is required by all living organisms. Zinc is used extensively in many biological processes, and alterations in zinc levels are implicated in the pathogenesis of numerous diseases, including AD. Since small fluctuations in brain zinc levels appear to effect AD progression, we investigated the zinc-related transcriptional responses in an AD versus non-AD state using microarray and RNA-sequencing (RNA-seq) datasets from cultured cells, mice, and humans. We identified 582 zinc-related differentially expressed genes (DEG) in human dorsolateral prefrontal cortex samples of late-onset AD (LOAD) versus non-AD controls, 146 zinc-related DEG in 5XFAD versus wild-type mice, and 95 zinc-related DEG in lipopolysaccharide (LPS)-stimulated N9 microglia versus unstimulated control cells, with 19 zinc-related DEG common to all three datasets. Of the 19 common DEG, functional enrichment and network analyses identified several biological processes and molecular functions, such as mRNA destabilization and nucleic acid binding, which may be important in neuroinflammation and AD development. Furthermore, therapeutic drugs targeting zinc-related DEG in the human dataset were identified. Taken together, these data provide insights into zinc utilization for gene transcription during AD progression which may further our understanding of AD pathogenesis and could identify new targets for therapeutic strategies targeted towards AD. |
| first_indexed | 2024-04-13T04:57:01Z |
| format | Article |
| id | doaj.art-5ac1b11013dc469bad0feac0cc348362 |
| institution | Directory Open Access Journal |
| issn | 2667-2421 |
| language | English |
| last_indexed | 2024-04-13T04:57:01Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj.art-5ac1b11013dc469bad0feac0cc3483622022-12-22T03:01:27ZengElsevierIBRO Neuroscience Reports2667-24212022-12-01133137Exploring the zinc-related transcriptional landscape in Alzheimer’s diseaseDaniel C. Shippy0Tyler K. Ulland1Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USACorresponding author.; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USAAlzheimer’s disease (AD) is a progressive neurological disorder, and increasing evidence suggests AD pathology is driven by metabolic dysfunction in the brain. Zinc is the second most abundant trace element found in the human body and is required by all living organisms. Zinc is used extensively in many biological processes, and alterations in zinc levels are implicated in the pathogenesis of numerous diseases, including AD. Since small fluctuations in brain zinc levels appear to effect AD progression, we investigated the zinc-related transcriptional responses in an AD versus non-AD state using microarray and RNA-sequencing (RNA-seq) datasets from cultured cells, mice, and humans. We identified 582 zinc-related differentially expressed genes (DEG) in human dorsolateral prefrontal cortex samples of late-onset AD (LOAD) versus non-AD controls, 146 zinc-related DEG in 5XFAD versus wild-type mice, and 95 zinc-related DEG in lipopolysaccharide (LPS)-stimulated N9 microglia versus unstimulated control cells, with 19 zinc-related DEG common to all three datasets. Of the 19 common DEG, functional enrichment and network analyses identified several biological processes and molecular functions, such as mRNA destabilization and nucleic acid binding, which may be important in neuroinflammation and AD development. Furthermore, therapeutic drugs targeting zinc-related DEG in the human dataset were identified. Taken together, these data provide insights into zinc utilization for gene transcription during AD progression which may further our understanding of AD pathogenesis and could identify new targets for therapeutic strategies targeted towards AD.http://www.sciencedirect.com/science/article/pii/S2667242122000410Alzheimer’s diseaseZincMicrogliaTranscriptomeNeuroinflammation |
| spellingShingle | Daniel C. Shippy Tyler K. Ulland Exploring the zinc-related transcriptional landscape in Alzheimer’s disease IBRO Neuroscience Reports Alzheimer’s disease Zinc Microglia Transcriptome Neuroinflammation |
| title | Exploring the zinc-related transcriptional landscape in Alzheimer’s disease |
| title_full | Exploring the zinc-related transcriptional landscape in Alzheimer’s disease |
| title_fullStr | Exploring the zinc-related transcriptional landscape in Alzheimer’s disease |
| title_full_unstemmed | Exploring the zinc-related transcriptional landscape in Alzheimer’s disease |
| title_short | Exploring the zinc-related transcriptional landscape in Alzheimer’s disease |
| title_sort | exploring the zinc related transcriptional landscape in alzheimer s disease |
| topic | Alzheimer’s disease Zinc Microglia Transcriptome Neuroinflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2667242122000410 |
| work_keys_str_mv | AT danielcshippy exploringthezincrelatedtranscriptionallandscapeinalzheimersdisease AT tylerkulland exploringthezincrelatedtranscriptionallandscapeinalzheimersdisease |