Mechanistic role of mesencephalic astrocyte-derived neurotrophic factor in myocardial ischemia/reperfusion injury
Year: 2024
Type: article
Abstract: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a protein crucial for cellular stress response and survival, particularly in the nervous and cardiovascular systems. Unlike traditional neurotrophic factors, MANF primarily regulates endoplasmic reticulum (ER) stress and protects cells by reducing ER stress-induced apoptosis. MANF operates both inside and outside cells, influencing key pathways like JAK/STAT and NF-κB to enhance cell survival during stress. Beyond its neuroprotective role, MANF is also vital in cardiovascular protection, mitigating damage by reducing inflammation and maintaining cellular function. Elevated MANF levels have been observed in patients experiencing myocardial infarction and murine models of ischemia-reperfusion (I/R) injury, highlighting its importance in these conditions. Overexpression of MANF in cardiomyocytes reduces ER-stress-induced cell death, while its depletion worsens this effect. Treatment with recombinant MANF (rMANF) has been shown to improve cardiac function in mice with I/R injury by decreasing infarct size and inflammation. Research also indicates that alterations in the α1-helix region of MANF can impact its structure, expression, secretion, and overall function. Given its protective effects and involvement in critical signaling pathways, MANF is being explored as a potential therapeutic target for ER stress-related diseases, including neurodegenerative disorders and cardiovascular conditions like myocardial I/R injury.
Source: Molecular Medicine
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,190
Awards: G1000608447, G1196682224, G1214234794, G1218068299, Molecular regulation of skeletal muscle thermogenesis, G1413706045, G1512127578, G1530010185, G186995139, Beta Cell Intracellular Calcium and Diabetes, Functional role of IP3 receptors in the regulation of cardiac myofibroblasts, G249311083, Modulation of Mitofusin Activity to Treat Heart Disease, G280444578, G281933567, G2836354684, G2940288175, A paradigm-shifting idea in storage-disease cardiomyopathy, G3074976661, G3672453180, Einstein-Montefiore Clinical and Translational Science Award Hub, Caspase-9 as a nodal point connecting necrotic and apoptotic cell death in myocardial infarction, Mechanisms of cardiovascular disease, G425922058, G4480573366, CTSA Administrative Supplement for Informatics Core: A novel AI/ML system to predict respiratory failure and ARDS in Covid-19 patients, G522617745, G5298350625, G531307636, G5423166509, G6295426566, G671159905, G6737277850, G7492960808, G7854002418, G790170206, G802470759, G8224181935, Purposeful Outreach for Diversity and Inclusion of Underrepresented in Medicine (PODIUM) Physician-Scientists, G8385843488, G8445767824, G864706750, G873634175, G9000020154, G9000036909, G9000045154, G9000045632, G9000148014, G9000203699, G9000291687, G981417163
OpenAlex ID: W4403781692