SERPINA3 (aka alpha-1-antichymotrypsin)

Abstract

Recent advances in proteomic, transcriptomic and genomic technologies have revealed much about the ACT protein and gene. In this review, we summarize our current understanding of the structure and potential physiological roles of the ACT protein, catalogue the regulatory elements that have been implicated in expression of the ACT gene, describe its tissue-specific expression and list the single nucleotide polymorphisms (SNPs) within the gene that track ACT variability. The ACT gene has been implicated in a number of complex human disorders and its potential involvement as a risk factor for Alzheimer's disease has been the subject of intensive research. However, due to previous limitations in methodologies and inadequate sample numbers the data has been conflicting with many studies failing to be replicated. In this regard, we highlight some potential approaches, which may prove to be beneficial in future studies.

A transcriptional signature of Alzheimer’s disease is associated with a metastable subproteome at risk for aggregation

“…These up-regulated genes are almost exclusively associated with an inflammatory response (Dataset S1). For example, of those genes that encode metastable proteins, the most highly up-regulated gene (123% increase in expression) in AD is alpha-1 antichymotrypsin, which inhibits serine proteases, particularly those active in inflammation (45).…”

Quantitative prediction of tumor response to neoadjuvant chemotherapy in breast cancer: novel marker genes and prediction model using the expression levels

“…DUSP2 may be involved in the response to this DNA damage stress. SERPINA3 is well known as a protease inhibitor that regulates the activity of cathepsin G in neutrophils and an estrogen-induced gene [31], and its expression was also reported as an indicator of good prognosis in estrogen receptor positive breast cancer [32]. Nevertheless, it will likely be very difficult to predict clinical therapeutic response by using a single marker alone, especially for combination regimens.…”

Molecular bases of neuroserpin function and pathology

“…Furthermore, it has been proven that NS is upregulated in brain of patients affected by Alzheimer's disease (77), and higher cerebrospinal fluid levels of NS in Alzheimer's patients were associated with the clinical diagnosis of the disease, facilitating its diagnostic classification (78). Notably, another serpin, a1-antichymotrypsin, is always found associated with Ab plaques in Alzheimer's patients (79). The role of a1-antichymotrypsin, however, is controversial because it has been proposed to either inhibit (80) or accelerate amyloid aggregation (81).…”