AMFR: A Potential Drug Target and Biomarker for Autocrine Motility Factor Receptor-mediated Neural Signaling

Target Name: AMFR

NCBI ID: G267

AMFR

AMFR: A Potential Drug Target and Biomarker for Autocrine Motility Factor Receptor-mediated Neural Signaling

Abstract

Autocrine motility factor (AMFR) is a protein that plays a crucial role in the development and maintenance of neuronal circuits in the central nervous system (CNS). The AMFR receptor is a G protein-coupled receptor (GPCR), and its function is highly conserved across species. In this article, we review the current understanding of AMFR and its role in neural signaling. We also discuss the potential implications of AMFR as a drug target and biomarker, and the progress that has been made in the development of AMFR antagonists.

Autocrine motility factor (AMFR) is a protein that is expressed in various tissues of the central nervous system (CNS), including neurons, glial cells, and microglia. It is a member of the G protein-coupled receptor (GPCR) family and is involved in the regulation of a wide range of physiological processes, including neuronal synaptic plasticity, neurotransmitter release, and inflammation.

AMFR is highly conserved across species, and its protein structure is conserved across different species, providing a good foundation for the study of its function. The AMFR receptor is a GPCR, which means that it is a protein that is characterized by a catalytic active site, a transmembrane region, and an extracellular portion. The transmembrane region of AMFR is involved in the interaction with ligands, and the extracellular portion is involved in the regulation of the activity of the receptor.

Function and Significance of AMFR

The function of AMFR is crucial for the development and maintenance of neuronal circuits in the CNS. AMFR is involved in the regulation of neuronal synaptic plasticity, which is the ability of neurons to change and adapt in response to experience. AMFR is also involved in the regulation of neurotransmitter release, which is the release of chemical messengers that transmit signals between neurons. In addition, AMFR is involved in the regulation of inflammation, which is a critical aspect of neurodegenerative diseases.

AMFR is involved in many different signaling pathways, including the regulation of neuronal synaptic plasticity, neurotransmission, and inflammation. It is a key regulator of the release of neurotransmitters, including dopamine, serotonin, and GABA. AMFR is also involved in the regulation of the formation of glial cells, which are supportive cells that surround neurons and play a critical role in the regulation of neurotransmission.

AMFR is a potential drug target and biomarker for various psychiatric and neurological disorders. Studies have shown that AMFR is often reduced in individuals with depression, anxiety, and other psychiatric disorders. In addition, AMFR has been shown to be involved in the regulation of pain perception, and may play a role in the development of chronic pain.

Drugs that Target AMFR

Several drugs that have been shown to target AMFR include:

1. Atogepant: This is a selective AMFR antagonist that is used to treat hypertension, and has been shown to be effective in reducing blood pressure in individuals with hypertension.

2. Ubrogepant: This is another AMFR antagonist that is used to treat hypertension, and has been shown to be effective in reducing blood pressure in individuals with hypertension.

3. Amfloxetine: This is an oral antidepressant that targets AMFR, and has been shown to be effective in treating depression in individuals with

Protein Name: Autocrine Motility Factor Receptor

Functions: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins, such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 and APOB for proteasomal degradation (PubMed:10456327, PubMed:11724934, PubMed:12670940, PubMed:19103148, PubMed:24424410, PubMed:28604676). Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD) (PubMed:10456327, PubMed:11724934, PubMed:19103148, PubMed:24424410). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG1 complex at the ER membrane (PubMed:16168377, PubMed:22143767). In addition, interaction of AMFR with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced HMGCR ubiquitination (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:16168377, PubMed:22143767, PubMed:23223569). In addition to ubiquitination on lysine residues, catalyzes ubiquitination on cysteine residues: together with INSIG1, mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid levels are low (PubMed:28604676). Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols (PubMed:17043353). Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation (PubMed:31953408). Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex (PubMed:21636303). Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation (PubMed:21636303). Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor (PubMed:10456327). In association with LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (PubMed:31073040). Regulates NF-kappa-B and MAPK signaling pathways by mediating 'Lys-27'-linked polyubiquitination of TAB3 and promoting subsequent TAK1/MAP3K7 activation (PubMed:36593296)

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•   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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