Detecting Oxidative Stress Biomarkers in Neurodegenerative Disease Models and Patients

Abstract

Oxidative stress is prominent in many neurodegenerative diseases. Along with mitochondrial dysfunction and pathological protein aggregation, increased levels of reactive oxygen and nitrogen species, together with impaired antioxidant defense mechanisms, are frequently observed in Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis. The presence of oxidative stress markers in patients’ plasma and cerebrospinal fluid may aid early disease diagnoses, as well as provide clues regarding the efficacy of experimental disease-modifying therapies in clinical trials. In preclinical animal models, the detection and localization of oxidatively damaged lipids, proteins and nucleic acids helps to identify most vulnerable neuronal populations and brain areas, and elucidate the molecular pathways and the timeline of pathology progression. Here, we describe the protocol for the detection of oxidative stress markers using immunohistochemistry on formaldehyde-fixed, paraffin-embedded tissue sections, applicable to the analysis of postmortem samples and tissues from animal models. In addition, we provide a simple method for the detection of malondialdehyde in tissue lysates and body fluids, which is useful for screening and the identification of tissues and structures in the nervous system which are most affected by oxidative stress.

Polystyrene Microplastics Exposure: An Insight into Multiple Organ Histological Alterations, Oxidative Stress and Neurotoxicity in Javanese Medaka Fish (Oryzias javanicus Bleeker, 1854)

“…The histological lesion of cerebral oedema was observed in the brain sections of Javanese medaka fish exposed to the highest concentration of PS-MPs. This may be due to increase in oxidative stress and oxidant damage observed in this study, which has been found to be implicated in several pathological conditions of the nervous system [ 32 , 33 , 34 ]. Another possible reason may be due to the ability of micro and nano-plastics taken up by aquatic organisms and mammals to reach the brain and exert a range of neurotoxic effects [ 47 ], however there is need for further exploration on the interaction of MPs and nervous system particularly the brain, as most studies focused on the gastrointestinal system.…”

“…The brain particularly is said to be at risk of lipid peroxidation and subsequent pathological processes in situations of impaired antioxidant defence mechanisms due to its high oxygen demand [ 32 , 33 ]. This is evident in neurodegenerative diseases, including Parkinson’s disease (PD), Huntington’s Disease (HD), Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), which presents with evidence of lipid peroxidation implicated by oxidative stress and damage [ 34 ].…”

A Review of Oxidative Stress Products and Related Genes in Early Alzheimer’s Disease

“…Obtaining patient material from the brain to allow insight into disease state is rather invasive and peripheral measurement of biomarker levels, such as in plasma or urine, are thus preferrable to obtain insight into oxidative stress in living patients. A protocol for the measurement of malondialdehyde in body fluids has been reported [ 266 ]. However, information on peripheral biomarker levels in relation to disease status and brain oxidative stress levels is limited and the observed lack of correlation of peripheral biomarker levels with oxidative stress status of the brain further hampers implementation of this route.…”

Bioactive peptides from nuts: A review

“…A state of oxidative stress causes damage at the cellular level, mainly affecting biomolecules, such as lipids, proteins, carbohydrates, and nucleotides, leading to multiple damages in tissues and organs and even apoptosis (Lobo et al ., 2010). Oxidative stress and inflammation pathways play an essential role in the mechanism of action of several chronic diseases, including several chronic degenerative diseases, including Alzheimer's, Parkinson's, Huntington's, diabetes, rheumatoid arthritis, neurodegenerative diseases, cancer, and even in natural processes, such as aging (Sidorova & Domanskyi, 2020). The modern and accelerated lifestyle in conjunction with the consumption of processed food, the lack of exercise, and long‐term exposure to a wide range of chemical and pro‐oxidant compounds leads to an increase of ROS in the body (Sharifi‐Rad et al ., 2020).…”