Neurodegenerative Disease Molecular Therapeutics based on Structural Activity Connections of Microglia Activation and Priming: A Comprehensive Review.

INTRODUCTION

In neurodegenerative diseases (NDDs) such as Alzheimer's (AD) and Parkinson's (PD), neuroinflammation plays a crucial role in the development and advancement of these disorders by contributing to the buildup of defective protein folding. Native immune response cells, known as microglial cells, enhance neuroinflammation by altering their shape and producing cytokines that promote inflammation. Inflammation in NDDs causes synapse pathology and dysfunction, although microglia-synapse relationships are unclear. Microglial structural activity alters physiology and architecture, causing functional changes and degeneration. Neurodegeneration and protein accumulation trigger microglial priming, which activates and regenerates microglia, resulting in heightened inflammatory responses. The biological activities and structural activation of microglia are studied to improve NDD therapy.

METHODS

An exhaustive search was conducted using the internet databases of PubMed, ScienceDirect, Google Scholar, DOAJ, and Wiley to identify any papers that discussed microglial activation, priming of this process, and molecular intervention in NDDs. First, molecular, preclinical, and clinical data were carefully reviewed for extraneous or redundant references, then narratively merged to offer a conceptual overlay.

RESULTS

This review examines the role of microglial cells in NDDs, highlighting potential interventions such as peptide- and RNA-based therapies, NF-κB, TLR4, JAK inhibitors, antibodies, and biologics.

DISCUSSION: The results suggest that stimulating microglial cells and enhancing neuron connections may improve treatment outcomes. The review indicates that translational research should be conducted to connect molecular pathways with clinically effective medicines.

CONCLUSION

Targeting microglia- and astrocyte-driven molecular markers could help resolve neuroinflammation and facilitate reliable therapeutic interventions in the progression of NDDs.