Chiang Mai Journal of Science

Neurodegenerative disorders (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), remain challenging to treat. Existing therapies provide only symptomatic relief and do not halt disease progression. This limitation has driven the search for multi-target neuroprotective agents, with growing attention to natural products. The medicinal fungus Ganoderma lucidum is notable for its diverse bioactivities. This review integrates and analyzes evidence for the neuroprotective effects of G. lucidum and related Ganoderma species, emphasizing mechanisms of action within a multi-targeted framework rather than merely cataloging reported effects. Preclinical studies indicate that bioactive compounds from Ganoderma, particularly polysaccharides and triterpenoids, act synergistically to counteract neurodegeneration by reducing oxidative stress and neuroinflammation, attenuating protein misfolding (Aβ, Tau, α-synuclein) and mitochondrial dysfunction, and modulating the gut-brain axis. The neuroprotective efficacy of Ganoderma extracts is highly dependent on extraction and processing methods, a factor often underemphasized in the literature. These findings require validation in standardized clinical trials, as robust preclinical evidence has not yet led to approved clinical therapies. This review also critically examines factors influencing the bioavailability, standardization, and cultivation practices of Ganoderma. This fungus is positioned not only as a traditional remedy but also as a promising candidate for future neurotherapeutic development, with its full therapeutic potential contingent upon well-controlled, rigorous clinical trials.