The Benefits of Natural Products for Neurodegenerative Diseases

Rashid, Mohammad Abdur, Haque, Mahmuda, Akbar, Mohammed, Mohammad Abdur Rashid Ph.D., Mahmuda Haque, Mohammed Akbar, Mohammad Abdur Rashid

M. Mohamed Essa, Mohammed Akbar, Gilles Guillemin

Oxidative stress in the brain is the major cause of neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases or amyotrophic lateral sclerosis. Under conditions of oxidative stress, the production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, resulting in the modification of macromolecules and their deposition in neuronal cell tissues. ROS plays an important role in neuronal cell death that they generate reactive aldehydes from membrane lipid peroxidation. Several neuronal diseases are associated with increased accumulation of abnormal protein adducts of reactive aldehydes, which mediate oxidative stress-linked pathological events, including cell growth inhibition and apoptosis induction. Combining findings on neurodegeneration and oxidative stress in Drosophila with studies on the metabolic characteristics of the human enzyme CBR1, it is clear now that CBR1 has a potential physiological role of neuroprotection in humans. Several studies suggest that CBR1 represents a significant pathway for the detoxification of reactive aldehydes derived from lipid peroxidation and that CBR1 in humans is essential for neuronal cell survival and to confer protection against oxidative stress-induced brain degeneration. Recently, it was discovered that HIF1alpha, AP-1, and Nrf2 could all regulate CBR1 at the transcriptional level. Nrf2 is known to regulate the transcription of antioxidant enzymes, and CBR1 functions as an antioxidant enzyme, suggesting that transcriptional regulation of CBR1 is a major contributor to the control of oxidative stress in neurodegeneration.