MAPK Signaling Dysregulation in Polycystic Ovary Syndrome: Crosstalk Networks, Biomarker Potential, and Therapeutic Targeting

Vollständiger Abstract

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Introduction: Polycystic ovary syndrome (PCOS) is a complicated endocrinemetabolic disorder that occurs in between 6-13% of women of reproductive age. There is a growing body of evidence that dysregulation of the mitogen-activated protein kinase (MAPK) signaling pathway is a major factor in the pathophysiology of PCOS. Methods: A narrative literature review was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. Original research articles, clinical studies, and relevant reviews in English were included, while duplicate, non-English, and irrelevant studies were excluded Results: There is evidence that MAPK kinase families, such as extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and phosphorylated p38 (p38), play a role in insulin resistance, hyperandrogenism, follicular dysfunction, and chronic inflammation in PCOS. Interactions with phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), mechanistic target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and nuclear factor kappa B (NF-κB) pathways and signals also enhance metabolic and reproductive pathological changes. Some molecules related to MAPK that include phosphorylated ERK and MAPK-associated microRNAs (miRNAs) have become diagnostic biomarkers. It is also shown through preclinical research that MAPK modulators have therapeutic effects, be it synthetic or natural compounds (curcumin, resveratrol, and berberine). Discussion: Modulation of the MAPK signaling pathway can be effective in treating the multifactorial PCOS. MAPK pathways can be modulated to enhance insulin sensitivity, lower androgen excess, and restore normal ovarian functioning. Conclusion: Altogether, MAPK signaling is a highly important molecular target in the pathogenesis of PCOS and can become an available biomarker and therapeutic target in the future, and be used in making a personalized treatment strategy