Neurodegenerative Diseases: Parkinson’s and Alzheimer’s Diseases
Oxidative stress and additional free radical generation catalyzed by the redox metals play important role in the neuro-degeneration and Mitochondrial dysfunctions and excitotoxicity result into the pathological conditions in each disease.
Abstract
Oxidative stress has been well implicated in the pathogenesis of various human diseases. Presently mechanistic considerations of the oxidative stress pathogenesis in most vital organ systems, e.g., nervous system, cardiovascular system, male/ female reproductive system, and autoimmune disease-related systems, will be discussed. The brain with major neurons and astrocytes is especially sensitive to the oxidative stress because of the lipid peroxidation in membranes containing high level of polyunsaturated fatty acids (PUFA). Oxidation of lipids, proteins, and DNA in neurons generates many by-products such as peroxides, alcohols, aldehydes, ketones, and cholesterol oxides which are toxic to the blood lymphocytes and macrophages, influencing the in vivo defense system (Ferrari 2000). ROS attacks proteins, oxidizing both the backbone and side chains, which in turn reacts with the amino acid side chain to form carbonyl functions. ROS attacks nucleic acids, causing DNA-protein cross-links and strand breaks, and modifies purine and pyrimidine bases resulting in the DNA mutations (Mattson 2003). ROS are particularly active in the brain and neuronal tissues as the excitatory amino acids and neurotransmitters, whose metabolism produces ROS, which serve as the sources of oxidative stress and result in neural damage. Most significant ill effect on the neurons takes place by dysregulation of the intracellular calcium signaling pathways initiated by the ROS in neuronal cell death (Ermak and Davies 2002). Excitotoxic effects initiated by the ROS induce intracellular calcium influx, leading to the activation of glutamate receptors and apoptosis in the neurodegeneration. All these insults ultimately reflect into the specific disorders. Oxidative stress has been linked to a range of chronic neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In these conditions, nerve cells in the brain and spinal cord are damaged or lost, leading to either functional loss (ataxia) or sensory dysfunction (dementia). Mitochondrial dysfunctions and excitotoxicity and finally apoptosis result into the pathological conditions in each disease (Gandhi and Abramov 2012). Neurodegeneration mediates a number of factors including the environmental and genetic predisposition. Oxidative stress and additional free radical generation catalyzed by the redox metals play important role in the neuro-degeneration. AD and PD being the main neurodegenerative disorders will be the special focus in the present write-up.