Human growth differentiation factor 15 (GDF-15) is a widely distributed protein that has shown to play multiple roles in both physiological and pathological conditions. In healthy individuals, GDF-15 is mainly expressed in the placenta, followed by the prostate, although low levels of expression have also been detected in different organs. GDF-15 acts through a recently identified receptor called glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) which signals through the rearranged during transfection (RET) tyrosine kinase receptor. The effects of GDF-15 are pleiotropic and include appetite regulation, and actions on metabolism, pregnancy, cell survival, immune response, and inflammation. GDF-15 also plays different roles in the pathophysiology of cardiovascular disease, autoimmunity, cancer-associated anorexia/cachexia, and diabetes. In recent years, several studies have reported a link between GDF-15 and the endocrine system. In this review, we up-date and summarize the relevant investigations of the relationships between GDF-15 and different endocrine conditions. We also assess the potential pathogenic role and potential therapeutic applications of GDF-15 in the field of endocrinology.
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http://dx.doi.org/10.1007/s12020-023-03377-9 | DOI Listing |
Neurogastroenterol Motil
January 2025
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Investigations into mechanisms of cyclic(al) vomiting syndrome (CVS) began at the bedside more than a century ago. The modern era started with the formation of the Cyclic Vomiting Syndrome Association in 1993 that helped initiate robust efforts in education, advocacy, family physician conferences, scientific symposia, dedicated clinical programs, therapeutic guidelines, and research. Even today, bedside clues continue to emerge with the recent description of cannabinoid hyperemesis syndrome (CHS) and subsequent evidence of a perturbed endocannabinoid system.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Background: Growth/differentiation factor-15 (GDF15) has been associated with dementia risk, yet its predictive value across cohorts and sub-population, as well as its relationship with endophenotypes relevant to dementia, remains unknown.
Methods: Using the Atherosclerosis Risk in Communities (ARIC) study as the discovery cohort, we examined the relationship between plasma GDF15 levels (SomaScan) and risk for incident all-cause dementia (ACD) in late-life (N=4,287, 7-year follow-up, M=75±5) and in midlife (N=11,595, 20-year follow-up, M=57±6). Utilizing the UK Biobank (UKB; replication cohort), we related plasma GDF15 (Olink) to incident ACD (N=35,673, 14-year follow-up, M=61±5), vascular dementia (VaD) and Alzheimer's disease dementia (AD).
Alzheimers Dement
December 2024
Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Background: Growth Differentiation Factor 15 (GDF15) is a TGF-beta superfamily protein upregulated during immune-mediated stress responses. Peripheral GDF15 is linked to adverse aging across organ systems including the brain. Immune dysregulation is implicated in frontotemporal dementia (FTD) pathogenesis.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Background: C-reactive protein (CRP) and growth differentiation factor 15 (GDF15) are important markers of inflammation associated with several aging-related morbidities. DNA methylation (DNAm) measures of CRP and GDF15 may provide stable epigenetic measures of chronic exposure to inflammation and could therefore be robustly predictive of inflammation-related brain aging and neurodegeneration.
Methods: Data from a subsample of cognitively normal older adults (n = 431) from the Baltimore Longitudinal Study of Aging with DNA methylation (DNAm) data and longitudinal structural neuroimaging (up to 8 visits, 16.
Curr Cardiol Rev
January 2025
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling.
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