Sentinels of neuroinflammation: the crucial role of myeloid cells in the pathogenesis of gliomas and neurodegenerative diseases

Abstract

Abstract The inflammatory processes that drive pathologies of the central nervous system (CNS) are complex and involve significant contributions from the immune system, particularly myeloid cells. Understanding the shared and distinct pathways of myeloid cell regulation in different CNS diseases may offer critical insights into therapeutic development. This review aims to elucidate the mechanisms underlying myeloid cell dysfunction and neuroinflammation in two groups of neurological pathologies with significant social impact and a limited efficacy of their treatments: the most common primary brain tumors –gliomas-, and the most prevalent neurodegenerative disorders -Alzheimer’s and Parkinson’s disease. Despite their distinct clinical manifestations, these diseases share key pathological features, including chronic inflammation and immune dysregulation. The role of myeloid cells in neuroinflammation has garnered special interest in recent years in both groups, as evidenced by the growing focus on therapeutic research centred on myeloid cells. By examining the cellular and molecular dynamics that govern these conditions, we hope to identify common and unique therapeutic targets that can inform the development of more effective treatments. Recent advances in single-cell technologies have revolutionized our understanding of myeloid cell heterogeneity, revealing diverse phenotypes and molecular profiles across different disease stages and microenvironments. Here, we present a comprehensive analysis of myeloid cell involvement in gliomas, Alzheimer’s and Parkinson’s disease, with a focus on phenotypic acquisition, molecular alterations, and therapeutic strategies targeting myeloid cells. This integrated approach not only addresses the limitations of current treatments but also suggests new avenues for therapeutic intervention, aimed at modulating the immune landscape to improve patient outcomes.

Keywords

• Myeloid cells
• Neuroinflammation
• Glioblastoma
• Alzheimer disease
• Clinical trials