"Neuroinflammation and Neurodegenerative Diseases: From Pathogenesis to Therapeutic Strategies"

Abstract

Neuroinflammation plays a central role in the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS). In this context, microglia and astrocytes are fundamental cells, capable of acting both in neuronal protection and injury. However, although frequently classified as neurotoxic (M1/A1) or neuroprotective (M2/A2) phenotypes, these categories do not fully represent the functional diversity and different inflammatory states observed throughout disease progression. The aim of this study is to review the main neuroinflammation mechanisms associated with neurodegenerative diseases, emphasizing the role of astrocytes and microglia, as well as describing biomarkers used in the assessment of inflammation in the central nervous system and possible emerging therapeutic strategies. A narrative literature review was conducted, including articles published between 2010 and 2025, selected from databases such as PubMed, Scopus, and Web of Science. The descriptors used included "neuroinflammation," "neurodegenerative diseases," "microglia," "astrocytes," and "biomarkers." Studies addressing inflammatory mechanisms, glial biomarkers, and therapeutic interventions aimed at modulating the neuroinflammatory response were included. Microglia and astrocytes play a dynamic role in the balance between neuroprotection and neurotoxicity. Continuous activation of these cells leads to the amplification of pro-inflammatory mediators, contributing to the progression of neurodegenerative diseases. Understanding glial plasticity and its different activation states is essential for the development of effective therapies, which must consider the stage of the disease and local inflammatory reactivity. Biomarkers that reflect glial activity emerge as promising tools for diagnosis, monitoring, and selection of targeted interventions. Thus, modulating the balance between pro-inflammatory and neuroprotective glial phenotypes represents a strategic path to slow neurodegenerative progression and improve future therapeutic approaches.