SERPINA3: Stimulator or Inhibitor of Pathological Changes

Abstract

SERPINA3, also called α-1-antichymotrypsin (AACT, ACT), is one of the inhibitors of serine proteases, one of which is cathepsin G. As an acute-phase protein secreted into the plasma by liver cells, it plays an important role in the anti-inflammatory response and antiviral response. Elevated levels of SERPINA3 have been observed in heart failure and neurological diseases such as Alzheimer’s disease or Creutzfeldt–Jakob disease. Many studies have shown increased expression levels of the SERPINA3 gene in various types of cancer, such as glioblastoma, colorectal cancer, endometrial cancer, breast cancer, or melanoma. In this case, the SERPINA3 protein is associated with an antiapoptotic function implemented by adjusting the PI3K/AKT or MAPK/ERK 1/2 signal pathways. However, the functions of the SERPINA3 protein are still only partially understood, mainly in the context of cancerogenesis, so it seems necessary to summarize the available information and describe its mechanism of action. In particular, we sought to amass the existing body of research focusing on the description of the underlying mechanisms of various diseases not related to cancer. Our goal was to present an overview of the correct function of SERPINA3 as part of the defense system, which unfortunately easily becomes the “Fifth Column” and begins to support processes of destruction.

Plasma proteome signature of canine acute haemorrhagic diarrhoea syndrome (AHDS)

“…SERPINA3 is also involved in tissue repair and remodelling, modulating tissue responses to injury, and promoting healing. Some studies have pointed out that SERPINA3 levels may be altered in specific cancer types and neurodegenerative diseases [22].…”

SMOC2, OGN, FCN3, and SERPINA3 could be biomarkers for the evaluation of acute decompensated heart failure caused by venous congestion

“…Serpin Family A Member 3 (SERPINA3), also known as α-1-antichymotrypsin (AACT or ACT), is part of the serpin superfamily, which primarily functions to inhibit serine proteases. This protein's elevated levels are observed in conditions such as heart failure and various neurological disorders, including Alzheimer's disease and Creutzfeldt-Jakob disease 46 . Research indicates that SERPINA3 acts as an endogenous gene responsive to the mineralocorticoid receptor and can be upregulated by aldosterone 47 .…”

Dispensable regulation of brain development and myelination by Serpina3n

“…Human SERPINA3 (also known as anti-chymotrypsin, ACT), one of the members of the serine protease inhibitor (Serpin) superfamily, is expressed mainly in the liver and brain under homeostasis (www.proteinatlas.org) and its primary molecular function of which is to inhibit the proteolytic activity of endogenous serine protease enzymes (Sanchez-Navarro et al, 2021). SERPINA3 is an acute phase glycoprotein that is secreted primarily by the liver to the bloodstream in response to injury/infection (Jain et al, 2011) and is elevated in the plasma and/or cerebrospinal fluid of patients affected by cancers (de Mezer et al, 2023) and neurological diseases/injuries such as Alzheimer’s disease (DeKosky et al, 2003) and multiple sclerosis (Fissolo et al, 2021). SERPINA3 also displays DNA binding properties and has been reported to function as a transcription regulator (Ko et al, 2019; Ko et al, 2018) and epigenetic modulator (Santamaria et al, 2013).…”