Abstract

Apoptosis, programmed cell death type I, is a critical part of neurodegeneration in cerebral ischemia, Parkinson’s, and Alzheimer’s disease. Apoptosis begins with activation of pro-death proteins Bax and Bak, release of cytochrome c and activation of caspases, loss of membrane integrity of intracellular organelles, and ultimately cell death. Approaches that block apoptotic pathways may prevent or delay neurodegenerative processes. Carotenoids are a group of pigments found in fruits, vegetables, and seaweeds that possess antioxidant properties. Over the last several decades, an increasing number of studies have demonstrated a protective role of carotenoids in neurodegenerative disease. In this review, we describe functions of commonly consumed carotenoids including lycopene, β-carotene, lutein, astaxanthin, and fucoxanthin and their roles in neurodegenerative disease models. We also discuss the underlying cellular mechanisms of carotenoid-mediated neuroprotection, including their antioxidant properties, role as signaling molecules, and as gene regulators that alleviate apoptosis-associated brain cell death.

Highlights

  • Apoptosis, programmed cell death type I, naturally occurs during development and maturation of the healthy brain [1,2]

  • Death receptor-mediated caspase 8 activation results in cleavage of B-cell lymphoma-2 (Bcl-2) interacting protein (Bid), a pro-apoptotic BH3-only protein, producing truncated Bid [3]. tBid is translocated to the mitochondrial membrane and recruits multidomain proapoptotic Bcl-2 proteins such as Bcl-2-associated X protein (Bax)

  • This study demonstrates that depletion of complex I decreases mitochondrial ATP production, increases mitochondria reactive oxygen species (ROS)

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Summary

Introduction

Apoptosis, programmed cell death type I, naturally occurs during development and maturation of the healthy brain [1,2]. Apoptotic pathways play an important role in brain-associated diseases that are caused by loss of functional populations of neurons. During neurotoxic stimulation, such as oxidative stress, excitotoxicity, or neuroinflammation, brain cells undergo death receptor-mediated (extrinsic) apoptosis, mitochondria-mediated (intrinsic) apoptosis, or a combination of both. Bcl-2 proteins, (2) increases mitochondrial membrane permeability, and (3) activates caspases in both mitochondria-dependent and independent manners. Autophagy and necrosis are involved during neurodegeneration, apoptotic features including increased abundance of pro-apoptotic Bcl-2 protein, activation of caspases, and cytochrome c release are found during progression of Parkinson’s disease [39,40,41]. Since neurodegeneration occurs gradually over a number of years, improving life-style factors like diet may delay apoptotic neuronal loss

Overview of Carotenoids
Lycopene
Astaxanthin
Lutein
Fucoxanthin
Conclusions
Methods

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