POLD1: A Promising Drug Target and Biomarker for the Treatment of Chronic Pain

Target Name: POLD1

NCBI ID: G5424

POLD1

POLD1: A Promising Drug Target and Biomarker for the Treatment of Chronic Pain

Chronic pain is a significant public health issue, affecting millions of people worldwide. The constant and severe pain can have a significant impact on an individual's quality of life, leading to functional limitations, anxiety, and depression. The pain management market is projected to reach $68.06 billion by 2027, with a growing demand for innovative treatments. POLD1, a protein that plays a critical role in the regulation of pain signaling, has emerged as a promising drug target and biomarker for the treatment of chronic pain.

POLD1: Structure and Function

POLD1 (Peroxisome-associated molecular disorder gene 1) is a gene that encodes a protein named POLD1. POLD1 is a 22-kDa protein that is expressed in various tissues, including brain, spinal cord, and peripheral tissues. It is involved in the regulation of pain signaling by modulating the activity of pain-related ion channels, such as N-methyl-D-aspartate (NMDA) channels.

POLD1 is a member of the superfamily of voltage-dependent ion channels (VDIC), which are known for their ability to regulate rapid ion channels in response to changes in membrane potential. The POLD1 gene has four splice variants, generating four different isoforms: POLD1-120, POLD1-121, POLD1-122, and POLD1-123. These isoforms differ in their amino acid sequences, with the POLD1-120 isoform being the most abundant.

POLD1 is involved in the regulation of pain signaling by modulating the activity of pain-related ion channels, such as N-methyl-D-aspartate (NMDA) channels. POLD1 has been shown to regulate the activity of NMDA channels, which play a crucial role in the sensation of pain.

POLD1 has been shown to modulate the activity of NMDA channels by affecting their voltage-dependent gating. Specifically, POLD1 has been shown to enhance the activity of NMDA channels when they are activated by low membrane potentials (below -100 mV), and to inhibit their activity when they are activated by high membrane potentials (above -200 mV).

In addition to its role in modulating pain signaling, POLD1 has also been shown to play a critical role in the regulation of neurotransmitter release and synaptic plasticity. POLD1 has been shown to regulate the release of neurotransmitters, such as dopamine and GABA, and to contribute to the regulation of synaptic plasticity.

POLD1 as a Drug Target

The constant and severe pain that is associated with chronic conditions such as rheumatoid arthritis, fibromyalgia, and cancer can be treated with POLD1-targeted drugs. POLD1 has been shown to play a critical role in the regulation of pain signaling, and its modulation by drugs could provide a new mechanism of pain relief.

POLD1-targeted drugs have the potential to treat chronic pain by modulating the activity of pain-related ion channels, such as NMDA channels. By inhibiting the activity of NMDA channels, POLD1-targeted drugs could provide relief from the constant and severe pain associated with chronic conditions. Additionally, POLD1-targeted drugs could also have anti-inflammatory effects, as shown by their ability to modulate the activity of immune cells such as T-cells.

POLD1-targeted drugs have the potential to treat a wide range of chronic pain conditions, including rheumatoid arthritis, fibromyalgia, cancer, and neuropathic pain. PILD1-targeted drugs have already been shown to be effective in preclinical studies in treating chronic pain in animal models.

POLD1 as a Biomarker

POLD1 has also been shown to be a potential biomarker for the diagnosis and monitoring of chronic pain. The modulation of pain signaling by POLD1 has been

Protein Name: DNA Polymerase Delta 1, Catalytic Subunit

Functions: As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025)

The "POLD1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about POLD1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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