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.
Highlights
Tumor necrosis factor receptor-associated protein 1 (TRAP1), 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
The HSP90 family is composed of three more isoforms, namely HSP90α and HSP90β located in the cytosol and glucose-regulated protein 94 (GRP94) present in the endoplasmic reticulum [1]
The mitochondrial chaperone TRAP1 is an important modulator of the mitochondrial energy metabolism including oxidative phosphorylation (OXPHOS) processes [9,31,35,36], and it operates by interacting with proteins of the mitochondrial electron transport chain (ETC), as well as succinate dehydrogenase (SDH) and cytochrome oxidase, known, respectively, as complex II and complex IV
Summary
Tumor necrosis factor receptor-associated protein 1 (TRAP1), 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. The prototypic HSP90 family member has three structural domains, namely, an N-terminal domain (NTD) responsible for ATP binding, a middle domain (MD) which is important for binding clients and the. TRAP1 was extensively studied in oncology once TRAP1 is selectively upregulated in several human tumors and this is correlated with malignant progression, metastatic potential, and resistance to chemotherapy [3]. For those reasons, TRAP1 is emerging as a therapeutic target with several researchers attempting to develop TRAP1 specific inhibitors. Mitochondrial TRAP1 is a cellular regulator of oxidative stress-induced cell death [4,5], mitochondrial homeostasis and bioenergetics [6] and unfolded protein response (UPR) in Antioxidants 2021, 10, 1829. We will explore the role of TRAP1 in neurodegenerative disorders and the potential of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
