Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases Article Swipe
Haruka Tsubaki
,
Ikuo Tooyama
,
Douglas G. Walker
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.3390/ijms21249357
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.3390/ijms21249357
The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer’s disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.
Related Topics
Concepts
TXNIP
Biology
Neurodegeneration
Thioredoxin
Cell biology
Thioredoxin-Interacting Protein
Inflammasome
Oxidative stress
Endoplasmic reticulum
Inflammation
Biochemistry
Medicine
Immunology
Internal medicine
Disease
Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms21249357
- https://www.mdpi.com/1422-0067/21/24/9357/pdf?version=1607490900
- OA Status
- gold
- Cited By
- 127
- References
- 171
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3111088764
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3111088764Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/ijms21249357Digital Object Identifier
- Title
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Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative DiseasesWork title
- Type
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reviewOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-12-08Full publication date if available
- Authors
-
Haruka Tsubaki, Ikuo Tooyama, Douglas G. WalkerList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms21249357Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/21/24/9357/pdf?version=1607490900Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://www.mdpi.com/1422-0067/21/24/9357/pdf?version=1607490900Direct OA link when available
- Concepts
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TXNIP, Biology, Neurodegeneration, Thioredoxin, Cell biology, Thioredoxin-Interacting Protein, Inflammasome, Oxidative stress, Endoplasmic reticulum, Inflammation, Biochemistry, Medicine, Immunology, Internal medicine, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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127Total citation count in OpenAlex
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2025: 20, 2024: 26, 2023: 41, 2022: 30, 2021: 10Per-year citation counts (last 5 years)
- References (count)
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171Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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