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Cited by 44Heat shock proteins researchMitochondrial Function and PathologyCell death mechanisms and regulation

TRAP1 in Oxidative Stress and Neurodegeneration

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Ramos Rego, Inês, Santos Cruz, Beatriz, Ambrósio, António Francisco, Alves, Celso Henrique·2021·Antioxidants
DOI 10.3390/antiox10111829PMC PMC8614808
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Abstract

Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and contributes to the maintenance of mitochondrial integrity even under cellular stress. TRAP1 is a cellular regulator of mitochondrial bioenergetics, redox homeostasis, oxidative stress-induced cell death, apoptosis, and unfolded protein response (UPR) in the endoplasmic reticulum (ER). TRAP1 has attracted increasing interest as a therapeutical target, with a special focus on the design of TRAP1 specific inhibitors. Although TRAP1 was extensively studied in the oncology field, its role in central nervous system cells, under physiological and pathological conditions, remains largely unknown. In this review, we will start by summarizing the biology of TRAP1, including its structure and related pathways. Thereafter, we will continue by debating the role of TRAP1 in the maintenance of redox homeostasis and protection against oxidative stress and apoptosis. The role of TRAP1 in neurodegenerative disorders will also be discussed. Finally, we will review the potential of TRAP1 inhibitors as neuroprotective drugs.

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Cited by

Sorted by citations

Authors
Ramos Rego, I., Santos Cruz, B., Ambrósio, A. F., & Alves, C. H.
Affiliations
  • Retinal Dysfunction and Neuroinflammation Lab, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University Coimbra, 3000-548 Coimbra, Portugal
  • Association for Innovation and Biomedical Research on Light and Image (PT)
Corresponding author
Alves, Celso Henrique
ORCID
Venue
Antioxidants
Publisher
MDPI AG
Published
2021-11-19
Volume
10
Issue
11
Pages
1829
ISSN
2076-3921 (ISSN-L)
DOI
10.3390/antiox10111829
PMC
PMC8614808
OpenAlex
W3214004285
Cited by
44
References
2
Citations by year
2026: 6 · 2025: 10 · 2024: 11 · 2023: 11 · 2022: 6
FWCI
0.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Antioxidants (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Estudo Geral (Universidad de Coimbra) (submittedVersion, cc-by)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders
Fundação para a Ciência e Tecnologia (Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020), Strategic Project UIDB/04539/2020 and UIDP/04539/2020 (CIBB),, CEECIND/00886/2017)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
TRAP1, Hsp90 chaperone, oxidative stress, neurodegeneration, redox homeostasis, apoptosis, unfolded protein response, neuroprotection, mitochondrial bioenergetics

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