Natural Bioactive Molecules as Neuromedicines for the Treatment/Prevention of Neurodegenerative Diseases

The brain is highly vulnerable to oxidative stress due to its elevated oxygen demand and abundance of oxidizable lipids (polyunsaturated fatty acids), which, alongside low endogenous antioxidant and regenerative capacities, contributes to neurodegenerative diseases (NDDs). Oxidative damage, neuroinflammation, excitotoxicity, and proteinopathy are central to the pathogenesis of disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis, Huntington’s disease (HD), and motor neuron diseases (MNDs). Naturally occurring bioactives—polyphenols, carotenoids, essential fatty acids, phytosterols, essential oils, and tocopherols—exhibit potent antioxidant and anti-inflammatory activities and multiple neuroprotective mechanisms. This Review examines their neuroefficacy and bioefficacy in supporting neurogenesis, neuroprotection, modulation of oxidative and inflammatory cascades, and mitigation/treatment of NDDs, highlighting evidence from in vitro, in vivo, and limited clinical studies.

FereshtehAfshin Babazadeh, Mohammadi Vahed, Qi Liu, Shahida Anusha Siddiqui, Mohammad Saeed Kharazmi, Seid Mahdi Jafari