<i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology
Alzheimer’s disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both pa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/10/1845 |
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| author | Edward O. Olufunmilayo R. M. Damian Holsinger |
| author_facet | Edward O. Olufunmilayo R. M. Damian Holsinger |
| author_sort | Edward O. Olufunmilayo |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both patients and caregivers. Numerous risk factors for the disease have been identified and our understanding of gene–environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of AD. Microglial cells, the innate immune cells of the central nervous system (CNS), have long been established as guardians of the brain by providing neuroprotection and maintaining cellular homeostasis. A protein with a myriad of effects on various important signaling pathways that is expressed in microglia is the Src Homology 2 (SH2) domain-containing Inositol 5′ Phosphatase 1 (SHIP1) protein. Encoded by the <i>INPP5D</i> (Inositol Polyphosphate-5-Phosphatase D) gene, SHIP1 has diminutive effects on most microglia signaling processes. Polymorphisms of the <i>INPP5D</i> gene have been found to be associated with a significantly increased risk of AD. Several studies have elucidated mechanistic processes by which SHIP1 exerts its perturbations on signaling processes in peripheral immune cells. However, current knowledge of the controllers of <i>INPP5D</i>/SHIP1 expression and the idiosyncrasies of its influences on signaling processes in microglia and their relevance to AD pathophysiology is limited. In this review, we summarize these discoveries and discuss the potential of leveraging <i>INPP5D</i>/SHIP1 as a therapeutic target for Alzheimer’s disease. |
| first_indexed | 2024-03-11T10:14:24Z |
| format | Article |
| id | doaj.art-0d9f77fbcf8348d980c8b0351db10327 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T10:14:24Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0d9f77fbcf8348d980c8b0351db103272023-11-16T10:29:31ZengMDPI AGGenes2073-44252023-09-011410184510.3390/genes14101845<i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease PathophysiologyEdward O. Olufunmilayo0R. M. Damian Holsinger1Laboratory of Molecular Neuroscience and Dementia, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, AustraliaLaboratory of Molecular Neuroscience and Dementia, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, AustraliaAlzheimer’s disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both patients and caregivers. Numerous risk factors for the disease have been identified and our understanding of gene–environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of AD. Microglial cells, the innate immune cells of the central nervous system (CNS), have long been established as guardians of the brain by providing neuroprotection and maintaining cellular homeostasis. A protein with a myriad of effects on various important signaling pathways that is expressed in microglia is the Src Homology 2 (SH2) domain-containing Inositol 5′ Phosphatase 1 (SHIP1) protein. Encoded by the <i>INPP5D</i> (Inositol Polyphosphate-5-Phosphatase D) gene, SHIP1 has diminutive effects on most microglia signaling processes. Polymorphisms of the <i>INPP5D</i> gene have been found to be associated with a significantly increased risk of AD. Several studies have elucidated mechanistic processes by which SHIP1 exerts its perturbations on signaling processes in peripheral immune cells. However, current knowledge of the controllers of <i>INPP5D</i>/SHIP1 expression and the idiosyncrasies of its influences on signaling processes in microglia and their relevance to AD pathophysiology is limited. In this review, we summarize these discoveries and discuss the potential of leveraging <i>INPP5D</i>/SHIP1 as a therapeutic target for Alzheimer’s disease.https://www.mdpi.com/2073-4425/14/10/1845SHIP1Alzheimer’s disease risk genesingle-nucleotide polymorphismmicroglia |
| spellingShingle | Edward O. Olufunmilayo R. M. Damian Holsinger <i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology Genes SHIP1 Alzheimer’s disease risk gene single-nucleotide polymorphism microglia |
| title | <i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology |
| title_full | <i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology |
| title_fullStr | <i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology |
| title_full_unstemmed | <i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology |
| title_short | <i>INPP5D</i>/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology |
| title_sort | i inpp5d i ship1 expression regulation and roles in alzheimer s disease pathophysiology |
| topic | SHIP1 Alzheimer’s disease risk gene single-nucleotide polymorphism microglia |
| url | https://www.mdpi.com/2073-4425/14/10/1845 |
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