Microglia activation and priming in neurodegenerative diseases reveal peptide, RNA, and inhibitor therapeutic targets

In neurodegenerative diseases (NDDs) like Alzheimer's (AD) and Parkinson's (PD), neuroinflammation significantly drives disease progression by contributing to defective protein folding. Microglial cells, the brain's native immune cells, exacerbate this inflammation by altering their morphology and producing pro-inflammatory cytokines. This inflammation leads to synapse pathology and dysfunction. Microglial priming, triggered by neurodegeneration and protein accumulation, activates and regenerates microglia, resulting in heightened inflammatory responses. Understanding microglial structural activity and biological functions is crucial for improving NDD therapies.

Researchers conducted an exhaustive narrative review, searching internet databases including PubMed, ScienceDirect, Google Scholar, DOAJ, and Wiley. The search focused on papers discussing microglial activation, priming of this process, and molecular interventions in neurodegenerative diseases (NDDs). Molecular, preclinical, and clinical data were carefully screened to remove extraneous or redundant references, then narratively merged to provide a conceptual overview of potential therapeutic strategies.

This comprehensive review elucidates the critical role of microglial cells in neurodegenerative diseases (NDDs), identifying several promising therapeutic interventions. These include peptide-based therapies, RNA-based therapies, and targeted inhibitors against key inflammatory pathways such as NF-κB, TLR4, and JAK. Additionally, antibodies and other biologics are highlighted as potential modulators of microglial activity. The review emphasizes that these approaches aim to resolve neuroinflammation by targeting microglia- and astrocyte-driven molecular markers. By understanding the structural activity and functional changes of microglia, the review suggests that specific molecular interventions can mitigate the detrimental effects of chronic neuroinflammation. This synthesis of evidence points towards a paradigm shift in NDD treatment, moving beyond symptomatic relief to address underlying inflammatory processes.

The review highlights that stimulating microglial cells and enhancing neuron connections are promising avenues for improving neurodegenerative disease treatment outcomes.