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Small Organic Compounds Mimicking the Effector Domain of Myristoylated Alanine-Rich C-Kinase Substrate Stimulate Female-Specific Neurite Outgrowth.

作者信息

Tschang Monica, Kumar Suneel, Young Wise, Schachner Melitta, Theis Thomas

机构信息

Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08554, USA.

Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08844, USA.

出版信息

Int J Mol Sci. 2023 Sep 19;24(18):14271. doi: 10.3390/ijms241814271.


DOI:10.3390/ijms241814271
PMID:37762575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10532424/
Abstract

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a critical member of a signaling cascade that influences disease-relevant neural functions such as neural growth and plasticity. The effector domain (ED) of MARCKS interacts with the extracellular glycan polysialic acid (PSA) through the cell membrane to stimulate neurite outgrowth in cell culture. We have shown that a synthetic ED peptide improves functional recovery after spinal cord injury in female but not male mice. However, peptides themselves are unstable in therapeutic applications, so we investigated more pharmacologically relevant small organic compounds that mimic the ED peptide to maximize therapeutic potential. Using competition ELISAs, we screened small organic compound libraries to identify molecules that structurally and functionally mimic the ED peptide of MARCKS. Since we had shown sex-specific effects of MARCKS on spinal cord injury recovery, we assayed neuronal viability as well as neurite outgrowth from cultured cerebellar granule cells of female and male mice separately. We found that epigallocatechin, amiodarone, sertraline, tegaserod, and nonyloxytryptamine bind to a monoclonal antibody against the ED peptide, and compounds stimulate neurite outgrowth in cultured cerebellar granule cells of female mice only. Therefore, a search for compounds that act in males appears warranted.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/7ab6a53de199/ijms-24-14271-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/8f339fc45901/ijms-24-14271-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/d54839c0c7d3/ijms-24-14271-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/4d69388254ce/ijms-24-14271-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/7ab6a53de199/ijms-24-14271-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/8f339fc45901/ijms-24-14271-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/d54839c0c7d3/ijms-24-14271-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/4d69388254ce/ijms-24-14271-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc86/10532424/7ab6a53de199/ijms-24-14271-g004a.jpg

相似文献

[1]
Small Organic Compounds Mimicking the Effector Domain of Myristoylated Alanine-Rich C-Kinase Substrate Stimulate Female-Specific Neurite Outgrowth.

Int J Mol Sci. 2023-9-19

[2]
Myristoylated alanine-rich C-kinase substrate effector domain peptide improves sex-specific recovery and axonal regrowth after spinal cord injury.

FASEB J. 2020-9

[3]
Functional role of the interaction between polysialic acid and myristoylated alanine-rich C kinase substrate at the plasma membrane.

J Biol Chem. 2013-1-17

[4]
Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions.

J Neurochem. 2016-1

[5]
The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C.

J Neurochem. 2017-8

[6]
Enhanced Neuronal Survival and Neurite Outgrowth Triggered by Novel Small Organic Compounds Mimicking the LewisX Glycan.

Mol Neurobiol. 2018-3-8

[7]
Inhibition of native and recombinant nicotinic acetylcholine receptors by the myristoylated alanine-rich C kinase substrate peptide.

J Pharmacol Exp Ther. 2008-12

[8]
A peptide against the N-terminus of myristoylated alanine-rich C kinase substrate promotes neuronal differentiation in SH-SY5Y human neuroblastoma cells.

J Vet Med Sci. 2024-11-1

[9]
Targeting the effector domain of the myristoylated alanine rich C-kinase substrate enhances lung cancer radiation sensitivity.

Int J Oncol. 2014-12-17

[10]
Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture.

J Neurochem. 2013-9-23

本文引用的文献

[1]
Effects of L1 adhesion molecule agonistic mimetics on signal transduction in neuronal functions.

Biochem Biophys Res Commun. 2023-1-29

[2]
Epigallocatechin gallate-derived carbonized polymer dots: A multifunctional scavenger targeting Alzheimer's β-amyloid plaques.

Acta Biomater. 2023-2

[3]
(-)-Epigallocatechin Gallate Attenuates Spinal Motoneuron Death Induced by Brachial Plexus Root Avulsion in Rats.

Curr Med Chem. 2022-8-15

[4]
Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro.

Biomolecules. 2022-3-12

[5]
Polysialic Acid in the Immune System.

Front Immunol. 2021

[6]
Epigallocatechin-3 gallate regulates macrophage subtypes and immunometabolism to ameliorate experimental autoimmune encephalomyelitis.

Cell Immunol. 2021-10

[7]
Epigallocatechin-3-Gallate Provides Protection Against Alzheimer's Disease-Induced Learning and Memory Impairments in Rats.

Drug Des Devel Ther. 2021

[8]
An assay for quantitative analysis of polysialic acid expression in cancer cells.

Carbohydr Polym. 2021-5-1

[9]
A cell-penetrating MARCKS mimetic selectively triggers cytolytic death in glioblastoma.

Oncogene. 2020-10-19

[10]
Functions of Small Organic Compounds that Mimic the HNK-1 Glycan.

Int J Mol Sci. 2020-9-24

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