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A Guide to Neurodegenerative Diseases and Oxidative Stress

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illness senior
Published on 15 November 2023

Neurodegenerative diseases can occur when nerve cells in the brain and the peripheral nervous system become damaged. Brain neurons cannot perform as they should, and our central nervous system (CNS) cannot function as it should.

People who suffer from a neurodegenerative disease can lose the ability to control their moods, have decreased cognitive abilities, and severely impaired memory. Worldwide, almost one in every six people (almost a billion people) is affected by a neurodegenerative disease.1

In this article, we will explore the link between neurodegenerative diseases and oxidative stress. If you are concerned about staying healthy as you age, this information can help you to manage your oxidative stress levels. Keeping your oxidative stress as low as possible may play a key role in reducing the chance of developing a mitochondrial or neurodegenerative disease.

 

What Is Oxidative Stress?

Oxidation is a normal bodily process that helps our CNS to fight off pathogens. Oxidation occurs when oxygen-containing molecules, known as free radicals, react with the oxygen in our bodies. When the production of free radicals exceeds the production of antioxidants, then oxidative stress can occur.2

Free radicals are reactive oxygen species (ROS) and reactive nitrogen species (RNS). During oxidation, a molecule will lose an electron and another molecule will acquire it. The molecule that gains the electron is said to be reduced. When oxidation and reduction occur simultaneously, it is called redox. Redox reactions are common in the body and have useful functions. Oxidative stress disrupts normal redox signalling. Dysfunctional redox signalling results in cell damage.

Because free radicals have an uneven number of electrons, they are highly reactive. An overload of free radicals means that the antioxidants cannot balance out their reactive effects. Without enough antioxidants, the reactive nature of free radicals can start to damage neurons, fatty tissue, cells, DNA, and proteins.

DNA, proteins and lipids abound in the body. Damage to DNA, proteins and lipids can cause a range of serious health issues. Patients with too much oxidative stress can develop a range of serious neurodegenerative diseases and mitochondrial diseases.

What Common Diseases are Linked to Oxidative Stress?

While it is a natural function with positive effects, too much oxidative stress has a range of negative impacts on our health. Oxidative stress contributes to premature ageing and can increase feelings of chronic fatigue and brain fog. Oxidative stress weakens our cells so they can’t fight off infections as effectively.

The main source of ROS in the vascular system is nicotinamide adenine dinucleotide phosphate oxidase enzymes, known as Nox enzymes. Nox enzymes are crucial for cellular signalling. Nox enzymes can also result in dysfunction leading to oxidative stress. Nox enzymes are a major cause of the development of arteriosclerotic disease.5

The accumulation of oxidative stress has been shown to cause cardiovascular diseases, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and some forms of cancer. Patients with oxidative stress have also been shown as more likely to develop diabetes, asthma, rheumatoid arthritis, and hypertension (high blood pressure).6,7

Oxidative stress has also been linked as a major factor in neurodegenerative diseases such as Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis, chronic depression and severe memory loss.8 Alzheimer’s disease is the most common neurodegenerative disease that is caused by oxidative stress.

The Link Between Alzheimer’s Disease and Oxidative Stress

The role oxidative stress has in neurodegenerative diseases such as Alzheimer’s disease has been well-researched and documented. Patients with Alzheimer’s disease have a significant imbalance in their redox state leading to oxidative stress.

During normal functioning, the mitochondrial electron transport chain uses most of the molecular oxygen with the rest being converted to hydrogen peroxide and superoxide radicals. In a state of oxidative stress, the body produces too much superoxide and hydrogen peroxide which can cause tissue damage which leads to adverse effects in the brain.

The brain requires lots of oxygen and has many peroxidation-susceptible lipid cells. Oxidative stress on CNS tissue can damage brain function via interacting mechanisms such as the release of excitatory amino acids and neurotoxicity. The body’s natural defences against oxidative stress can alter the structure of crucial molecules and further damage the brain. The large amounts of reactive oxygen species (ROS) formed in the mitochondria by oxidative stress have been shown to dramatically increase the risk of patients developing Alzheimer’s disease.9

What is the Role of ROS in Neurodegenerative Diseases?

There is one subset of free radicals that are believed to cause more damage than others and play a greater role in the development of neurodegenerative diseases and mitochondrial diseases. Known as reactive oxygen species (ROS), these free radicals are produced when the body metabolises oxygen. ROS help the body fend off microorganisms and play a role in cellular signalling. A build-up of ROS, however, can contribute to increased levels of oxidative stress.4

One of the main sources of the production of ROS free radicals is a process known as mitochondrial oxidative phosphorylation.3 Mitochondria produce the energy we need to function. If the body’s DNA cannot communicate with mitochondria, then mitochondrial dysfunction can occur. Malfunctioning mitochondria can cause damage to cells and cause them to die early. Patients that suffer from neurodegenerative diseases often develop secondary mitochondrial dysfunction.

What Causes an Accumulation of Oxidative Stress?

Our bodies produce free radicals to break down nutrients to help give us the energy we need. They’re part of the normal metabolic process of the body. As we age the accumulation of free radicals within our bodies increases. This is one of the reasons why we become more predisposed to neurodegenerative diseases such as Alzheimer’s disease as we become older.

Environmental factors can also cause the body to produce too many free radicals and go into a state of oxidative stress. Being exposed to carcinogens can cause the body to create excess free radicals. Prolonged exposure to tobacco smoke or air pollution can result in the overproduction of free radicals. Other causes include overexposure to ultraviolet radiation in sunlight and overexposure to radon, radiation, and ozone. Some pesticides and industrial chemicals can be carcinogenic and are known to cause a build-up of free radicals that leads to oxidative stress.

Who Is Most at Risk of Developing Oxidative Stress?

As we age our bodies naturally become less efficient. Our physiological and biochemical processes slow down and we become more likely to develop diseases. Studies show that the progress of ageing and the onset of diseases related to advancing age can be linked to increased levels of oxidative stress.10 Older people are at the most risk of developing oxidative stress and the health conditions associated with oxidative stress.

Other people who are at risk of oxidative stress include:

  • Cancer patients
  • Smokers
  • Alcoholics or heavy drinkers
  • People who are obese or overweight
  • People who are overexposed to sunlight
  • People who exercise in excess
  • People on certain types of medication
  • People who are exposed to air pollution
  • People whose diet includes large amounts of sugar and fats
  • People who work with industrial chemicals, pesticides, or industrial cleaning products

How to Reduce Oxidative Stress and the Risk of Alzheimer’s Disease

We cannot completely remove free radicals from our systems and thus avoid oxidative stress altogether. There are certain steps we can take to limit the number of free radicals our bodies produce and reduce the likelihood of oxidative stress and developing associated conditions such as Alzheimer’s disease.

Adjusting your diet so that you consume more foods that contain antioxidants can help to combat the build-up of free radicals. Eating a variety of fruits and vegetables every day will help to increase the antioxidants in your body. Some foods are higher in antioxidants than others. Try and add the following antioxidant-rich foods to your diet:

  • Dark chocolate
  • Blueberries
  • Pecan nuts
  • Artichokes
  • Strawberries
  • Raspberries
  • Red cabbage
  • Kale
  • Spinach
  • Beans
  • Green tea
  • Garlic
  • Turmeric

Avoid overeating or binge eating. Quitting smoking and limiting the amount of alcohol you drink will also help to stop the accumulation of free radicals in your body. Exercise regularly at a moderate level and take steps to ensure you get enough sleep. Wear sunscreen and limit your exposure to direct sunlight. If you work with chemicals, radiation, or pesticides ensure you wear adequate personal protective equipment.

Conclusion

Oxidative stress is a major cause of neurodegenerative diseases such as Alzheimer’s disease, ALS, and Parkinson’s disease. While oxidative stress is a natural process and plays a normal role in the ageing process, it can damage our cells and CNS.

Older people naturally produce more free radicals so are more susceptible to oxidative stress and the associated neurodegenerative diseases. Maintaining a healthy weight and lifestyle, exercising regularly, limiting prolonged exposure to direct sunlight and chemicals, quitting smoking, and drinking in moderation can reduce the free radicals in our bodies. This in turn will reduce the likelihood of experiencing a condition induced by oxidative stress.

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Sources
1 https://news.un.org/en/story/2007/02/210312
2 PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551541/ DOI: 10.1155/2017/8416763
3 PubMed: https://pubmed.ncbi.nlm.nih.gov/22729852/ DOI: 10.1007/978-1-4614-3573-0_1
4 https://www.sciencedirect.com/science/article/abs/pii/S1359644620305225
5 PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745500/ DOI: 10.3390/antiox6040090
6 PubMed: https://pubmed.ncbi.nlm.nih.gov/29731617/ DOI: 10.2147/CIA.S158513
7 PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612399/ DOI: 10.1155/2019/7092151
8 PubMed: https://pubmed.ncbi.nlm.nih.gov/15031734/ DOI: 10.1038/nrd1330
9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840676/
10 PubMed:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574639/ DOI: 10.1002/agm2.12121