Emerging Natural and Synthetic Neuroactive Compounds in the Management of Neurodegenerative Diseases: Mechanistic...

Degenerative neurological diseases (DNDs) represent a group of progressive disorders characterized by the gradual loss of neuronal structure and function, leading to cognitive and motor impairments. Despite advances in symptomatic management, there remains a significant unmet clinical need for effective disease-modifying therapies. Neuroactive compounds, which are agents capable of modulating neuronal signaling and cellular processes in the central nervous system, have attracted increasing attention as potential therapeutic candidates. These compounds, including natural and synthetic molecules, target diverse biological pathways and offer a promising approach to addressing the complexity of neurodegenerative diseases.

Major scientific databases and research platforms, including PubMed, Google Scholar, ResearchGate, Scopus, Web of Science, ScienceDirect, and the Cochrane Library, were used to conduct a comprehensive literature search. Keywords used were "Neurological Disease", "neuroprotective compounds", "Neurodegenerative pathways", "protein misfolding", "oxidative stress", "neuroinflammation", and "Mechanism of compounds" to find peer-reviewed publications.

These compounds include small-molecule modulators of neurotransmitter targets, phytochemicals derived directly from plants, synthetic and endogenous neurosteroids, synthetic and native peptides and growth factors, and microbiota-derived metabolites and nanocarrier agents, such as extracellular vesicles. Together, these agents demonstrate neuroprotective and neurorestorative properties through the mitigation of oxidative stress, reduction of inflammatory responses, improvements in mitochondrial function, induction of autophagy/proteostasis, modulation of synaptic plasticity/neurogenesis, and glial-neuron interactions.

Despite promising preclinical studies, successful conversion in a clinical setting remains challenging due to poor blood-brain barrier permeability, low bioavailability, disease heterogeneity, and the lack of appropriate models.

This review summarizes recent developments in neuroactive compounds, the underlying pathophysiological processes, and core issues in translating them into useful diseasemodifying therapies for patients with neurodegenerative diseases.