Mitochondria and Neurodegenerative Diseases

Oxidative stress is considered to be a key contributor to the onset and progression of many neurological disorders. Oxidative stress results when the production of reactive oxygen species (ROS) exceeds elimination by antioxidant pathways. The brain, with its high metabolic rate and oxygen consumption, is particularly susceptible to oxidative stress. The brain also has limited antioxidant defense mechanisms compared to other tissues. 

Mitochondrial DNA (mtDNA) in the brain is especially vulnerable to oxidative damage as a result of the proximity of mtDNA to the respiratory chains, which are the primary cellular generators of ROS. Under physiologic conditions, mtDNA damage and repair are balanced, but if mtDNA repair is defective or oxidative damage exceeds the

repair capacity, damage becomes permanent

and leads to impairment of cellular metabolism.

 

Since neurons are post-mitotic and do not replicate, there is limited capacity for regeneration in the adult nervous system. A significant amount of mtDNA damage leads to selective loss of  neurons, a key factor in aging and neurodegeneration. 

 

The brain, therefore, requires significant DNA repair activity to prevent the type of damage that leads to neurodegenerative disease. The most common oxidative mtDNA lesion is 8-oxoguanine (8-oxoG), and one of the key BER enzymes responsible for repair of oxidized mtDNA is 8-oxoguanine DNA glycosylase (OGG1). 

Learn more about mitochondrial damage and neuroinflammation

 

Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia in adults, especially in people aged 65 years or over.  AD is currently estimated to affect over 44 million people worldwide, with this number expected to double every 20 years.

Learn more about Alzheimer's disease.

Parkinson’s Disease

Parkinson’s disease (PD), with a prevalence of 2% of the population over the age of 65, is one of the most common neurodegenerative disorders and is characterized by resting tremor, rigidity, and bradykinesia.

Learn more about Parkinson's disease.

DNA Repair Volumes 91–92, July–August 2020, 102871

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