Natural Compounds as Modulators of Neurosteroidogenesis: Therapeutic Perspectives in Neurodegenerative Diseases

Neurodegenerative diseases represent a major and growing health challenge, characterized by progressive neuronal dysfunction and loss, accompanied by complex pathological processes that remain incompletely understood. Despite advances in therapeutic research, effective strategies capable of modifying the underlying mechanisms of neurodegeneration remain limited. Increasing evidence suggests that neurosteroids, endogenous steroidal compounds synthesized within the nervous system, play important roles in the regulation of neuronal function, synaptic activity, neuroinflammation, oxidative stress, mitochondrial function, and neuronal survival. Neurosteroidogenesis is a tightly regulated process involving the enzymatic conversion of cholesterol and steroid precursors into biologically active neurosteroids. Alterations in this pathway have been associated with disturbances in neural homeostasis and may contribute to mechanisms underlying neurodegenerative processes. Consequently, modulation of neurosteroidogenesis represents a potential therapeutic approach for promoting neuronal resilience and maintaining nervous-system function. This thesis aims to provide a comprehensive investigation of the potential of natural compounds as modulators of neurosteroidogenesis and to evaluate their therapeutic relevance in the context of neurodegenerative diseases. Particular emphasis will be placed on the biochemical pathways involved in neurosteroid synthesis and metabolism, the enzymes and regulatory mechanisms controlling these pathways, and the molecular mechanisms through which natural compounds may influence neurosteroidogenic processes. The relationship between neurosteroidogenic modulation and key mechanisms involved in neurodegeneration, including neuroinflammation, oxidative imbalance, mitochondrial dysfunction, impaired neuronal signaling, and neuronal loss, will also be examined. Through an integrated analysis of the available scientific literature and experimental evidence, this work aims to clarify the potential role of natural compounds in regulating neurosteroidogenesis and to identify the molecular pathways that may underlie their neuroprotective effects. The thesis will also consider current limitations, gaps in knowledge, and challenges associated with translating neurosteroidogenic modulation into therapeutic applications. Overall, this work seeks to contribute to a better understanding of neurosteroidogenesis as a potential therapeutic target and to provide a scientific framework for the further investigation of natural compounds as promising modulators of neurosteroid-related pathways in neurodegenerative disorders.