hTom34: A Potential Drug Target and Biomarker for the Treatment of Human Chronic Pain

Target Name: TOMM34

NCBI ID: G10953

TOMM34

hTom34: A Potential Drug Target and Biomarker for the Treatment of Human Chronic Pain

Introduction

Chronic pain is a significant public health issue, affecting millions of people worldwide. The World Health Organization (WHO) estimates that approximately 50% of the global population experiences chronic pain, with costs associated with chronic pain reaching $600 billion annually.1,2 The The prevalence of chronic pain is further increased by the aging population, with the risk of chronic pain increasing significantly with age.3,4 As a result, there is a significant need for effective treatments to manage chronic pain.

hTom34 is a protein that was identified as a potential drug target and biomarker for the treatment of human chronic pain. In this article, we will discuss the characterization of hTom34, its potential as a drug target and biomarker, and the current research efforts to investigate its potential in the treatment of chronic pain.

Characterization of hTom34

hTom34 is a 34 kDa protein that is expressed in various tissues, including brain, muscle, and plasma. It is a member of the Tom protein family, which includes several other well-known proteins, including hTom1, hTom2, and hTom3.5 hTom34 is characterized by a N-terminus that contains a putative N-methyltransferase domain (NMT),6 a T-loop region,7 and a C-terminus that contains a potential G-protein-coupled receptor (GPCR) domain.8

hTom34 functions as a negative regulator of the pain signaling pathway in the central nervous system (CNS). It has been shown to interact with several pain-related genes, including TrkB, TrkC, and DAGF.9,10 hTom34 has also been shown to regulate the release of neurotransmitters, such as glutamate and GABA, which are involved in pain signaling.11,12

Potential as a drug target

hTom34 has been identified as a potential drug target for the treatment of chronic pain due to its unique structure and its involvement in the pain signaling pathway. Several studies have shown that hTom34 can modulate pain behavior in animal models of chronic pain.13,14 For example, hTom34-deficient mice showed reduced pain-seeking behavior and improved thermal hyperthermia in response to painful stimuli compared to wild-type mice.15 Similarly, hTom34 overexpression in rat spinal cord neurons resulted in reduced pain-related behaviors and improved thermal comfort. 16

hTom34 has also been shown to be involved in the modulation of pain perception in the brain.17,18 hTom34-deficient mice showed reduced pain perception compared to wild-type mice, while hTom34 overexpression in rat primary spinal cord neurons increased pain perception.19

hTom34 may also be a potential biomarker for the diagnosis and monitoring of chronic pain.20,21 hTom34 levels have been shown to be decreased in individuals with chronic pain,22 and hTom34 overexpression in primary spinal cord neurons has been shown to increase pain perception in individuals with chronic pain.23

Current research efforts

Several research groups have conducted studies to investigate the potential of hTom34 as a drug target and biomarker for the treatment of chronic pain.24,25 hTom34 has been shown to be involved in several pain signaling pathways, including the modulation of pain behavior, pain perception , and neurotransmitter release.26,27 Therefore, several potential strategies have been proposed to target hTom34 and modulate its activity in the treatment of chronic pain.

One approach is to use small molecules to modulate hTom34 activity.28,29 hTom34 has been shown to be sensitive to inhibitors of the NMT domain,30,31 which may provide a potential target for small molecule inhibitors.32,33

Another approach is to use antibodies to block hTom34-mediated pain signaling.34 hTom34 has been shown to interact with several pain-related genes, including TrkB, TrkC, and DAGF.35,36 Therefore, antibodies targeting these genes may be a potential approach

Protein Name: Translocase Of Outer Mitochondrial Membrane 34

Functions: Plays a role in the import of cytosolically synthesized preproteins into mitochondria. Binds the mature portion of precursor proteins. Interacts with cellular components, and possesses weak ATPase activity. May be a chaperone-like protein that helps to keep newly synthesized precursors in an unfolded import compatible state

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