Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances

Background: Neurodegenerative diseases (NDDs) are a diverse group of neurological disorders with progressive neuronal loss at specific brain regions, leading to impaired cognitive functioning, loss of neuroplasticity, severe neurological impairment, and dementia. The incidence of neurodegenerative diseases is increasing at an alarming rate with current treatments struggling to barely prolong the inevitable. The desperation to discover a therapeutic agent to treat neurodegenerative diseases and to aid in the process of healthy recovery has opened a gateway into natural pigments. Hypothesis: The xanthophyll pigment lutein may bear the potential as a therapeutic agent against NDDs. Results: Lutein plays an important role in brain development, cognitive functioning, and improving neuroplasticity. In vitro and in vivo studies revealed the neuroprotective properties of lutein against NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. The neuroprotective effect of lutein is evidenced by the reduction of free radicals and the simultaneous strengthening of the endogenous antioxidant systems by activating the NRF-2/ERK/AKT pathway. Further, it effectively suppressed mitochondrial aberrations, excitotoxicity, overaccumulation of metals, and its resultant complications. The immunomodulatory activity of lutein prevents neuroinflammation by hindering NF-kappa B nuclear translocation, regulation of NIK/IKK, PI3K/AKT, MAPK/ERK, JNK pathways, and ICAM-1 downregulation. Lutein also rescued the dysregulated cholinergic system and resolved memory defects. Along with its neuroprotective properties, lutein also improved neuroplasticity by enabling neurogenesis through increased GAP-43, NCAM, and BDNF levels. Conclusion: Lutein exhibits strong neuroprotective activities against various NDDs. Though the investigations are in the exploratory phase, this review presents the consolidation of scattered evidence of the neuroprotective properties of lutein and urges its further exploration in clinical studies.