Molecular Signaling Pathways in Depression and Neuroinflammation: Focus on New Pathophysiological Proteins and...

Neuroinflammation is a multifaceted process in which specific biomolecules (such as pro-inflammatory cytokines and signaling proteins) act as primary mediators of neuropsychiatric disorders, including depression. Despite growing evidence, the precise interconnected cascades within these neuroinflammatory signaling pathways and their regulatory proteins remain to be fully elucidated, which presents a significant unmet need for targeted therapeutic strategies with clear mechanistic validation. Accordingly, the present review analyzes the impact of neuroinflammation on the pathophysiology of depression in various rodent models. We explore the regulatory mechanisms by which factors such as oxidative stress, calcium signaling, and inflammasome-mediated inflammation affect neurotransmitter synthesis and neuronal integrity. Furthermore, we elucidate the therapeutic potential of synthetic compounds and naturally derived agents targeting these specific molecular pathways. Based on a systematic literature search, this review focuses exclusively on pharmacological agents with clearly defined molecular mechanisms and rigorous depression-associated in vivo validation, thereby providing promising therapeutic strategies for the restoration of neurobiological homeostasis.