Neuroinflammation in diabetes: from pathophysiological mechanisms to therapeutic opportunities

Abstract

Diabetes is increasingly recognized as a systemic metabolic disease with significant consequences beyond glycemic dysregulation, including a growing impact on brain structure and function. Among the mechanisms involved in this process, neuroinflammation has emerged as a central biological axis that links chronic metabolic stress with neuronal injury, cognitive decline, and broader nervous system dysfunction. Rather than representing an isolated consequence of hyperglycemia, diabetes-associated neuroinflammation reflects the convergence of blood–brain barrier disruption, glial activation, innate immune signaling, oxidative stress, mitochondrial dysfunction, and inflammasome activation. These interconnected processes reinforce each other and contribute to the transition from adaptive neuroimmune responses to chronic pathogenic inflammation. In this review, we synthesize current evidence on cellular and molecular mechanisms that connect diabetes with neuroinflammatory signaling, highlighting key pathophysiological processes and their therapeutic implications. We also analyzed current and emerging therapeutic approaches, including conventional pharmacological agents and natural compounds with anti-inflammatory and neuroprotective potential. Taken together, the available evidence supports the view that diabetes-associated neuroinflammation is a multidimensional and therapeutically relevant process that should be studied further to provide opportunities in identifying new biomarkers related to the mechanistic stratification of the process, and to design new neuroprotective interventions, which could also contribute significantly to healthy aging.

Keywords: Diabetes mellitus, neuroinflammation, blood–brain barrier, microglia, oxidative stress