ING Proteins and Neural Development in Newborns from Alcohol- and/or Drug-Abusing Pregnant Women

Maternal consumption of alcohol and drugs during pregnancy can compromise neural development with long-lasting impact on individuals' health. The inhibitor of growth (ING) family of proteins is an epigenetic regulator that plays a central role in fetal brain development, contributing to neural stem cell maintenance, neuronal differentiation, and the regulation of genes involved in brain morphogenesis. Given the susceptibility of the developing nervous system to epigenetic dysregulation induced by alcohol and drugs, this narrative study aims to summarize literature evidence with the hypothesis that ING proteins may represent a critical but understudied mechanistic link between maternal substance dependence and adverse neurodevelopmental outcomes in newborns. We conducted a comprehensive literature search across three databases (PubMed, Scopus, and Web of Science) up to February 2026 to identify relevant studies. Search terms included combinations of "ING proteins", "neural development", "alcohol", "drugs", "epigenetic", "oxidative stress" and "neuroinflammation". The inclusion criteria were limited to original studies published in English that examined neural development in newborns; the exclusion criteria encompassed non-English publications, letters, editorials, and case reports, and those not directly addressing the specified topics. We identified 55 papers; six were excluded per the exclusion criteria, leaving 49 works discussed in this review. ING proteins are epigenetic regulators essential for embryonic and neural development, including neural stem cell fate and neurogenesis, while substances of abuse are disruptors of the essential pathways necessary for the right fetal brain development. Furthermore, substance abuse creates oxidative stress environments and activates pathways that require ING-mediated chromatin regulation. ING proteins likely act as mediators linking oxidative stress, neuroinflammation, and transcriptional reprogramming in the developing brain. Meanwhile, alcohol and drugs induce epigenetic reprogramming that may disrupt ING-mediated chromatin control. There is little evidence directly linking prenatal exposure (e.g., alcohol and drugs) to ING changes during fetal development. However, we hypothesize that ING proteins function as epigenetic stress response regulators whose disruption by oxidative stress, inflammation, and chromatin alterations induced by prenatal alcohol or drug exposure may contribute to impaired fetal neurodevelopment. Although direct experimental evidence remains limited, this could be a promising and relatively unexplored research area.