Neuroinflammation at the crossroads of metabolic and neurodegenerative diseases: Causes, consequences and interventions

Neuroinflammation is increasingly recognized as a pivotal factor not only in neurodegenerative diseases such as Alzheimer and Parkinson, but also in the pathogenesis of metabolic disorders that influence or exacerbate these conditions. This review explores the intricate relationships between neuroinflammation, metabolic dysregulation and neurodegenerative diseases. We begin by detailing the fundamental mechanisms of neuroinflammation, focusing on the roles of astrocytes and microglia, and the molecular pathways that contribute to inflammatory processes in the CNS. The discussion then shifts to how metabolic abnormalities such as obesity, insulin resistance and dyslipidemia can initiate or perpetuate neuroinflammatory responses. Furthermore, we examine the evidence linking neuroinflammation to various neurodegenerative diseases, delineating how inflammatory processes can exacerbate neurodegeneration through feedback loops that impair neuronal function and survival. We also review clinical and preclinical studies that provide insights into the bi-directional interactions between neurodegeneration and metabolic health. This includes a critical evaluation of current therapeutic strategies targeting neuroinflammation, ranging from conventional anti-inflammatory treatments to innovative approaches aimed at modulating metabolic factors. Lastly, the review identifies promising therapeutic avenues, challenges in current treatment paradigms, and the potential for integrative interventions that address both metabolic and inflammatory components. Our goal is to emphasize the need for comprehensive strategies that consider the complexity of these intertwined systems in the treatment of neurodegenerative and metabolic diseases.