Affiliations: Department of Biochemistry, Science College, King Saud
University, P.O. Box 22452, 11495, Riyadh, Saudi Arabia. Tel.: +966 1 4682184;
Fax: +966 1 4769137; E-mail: elansary@ksu.edu.sa
Abstract: An unavoidable consequence of aerobic respiration is the generation
of reactive oxygen species (ROS). ROS is a collective term that includes both
oxygen radicals and certain oxidizing agents that are easily converted into
radicals. They can be produced from both endogenous and exogenous substances.
ROS play a dual role in biological systems, since they can be either harmful or
beneficial to living systems. They can be considered a double-edged sword:
oxygen-dependent reactions and aerobic respiration have significant advantages
but overproduction of ROS, a consequence of oxygen-dependent reactions, has the
potential to cause damage. Overproduction of ROS may negatively impact neonatal
growth and contribute to the aetiology of many developmental disorders. During
mitochondrial respiration, an inability to neutralize reactive oxygen species
and free radicals leads to oxidative stress. The inner membrane of the
mitochondria contains a large number of free radical scavengers including
glutathione, vitamin C, and vitamin E, as well as anti-oxidant enzymes such as
superoxide dismutase. The brain is particularly vulnerable to free radical
attack for several reasons, including exposed to high oxygen concentrations,
relatively low antioxidant protection, membranes with high levels of
polyunsaturated fatty acids, and high iron and ascorbate content. The brain's
high energy demand is primarily supplied by oxidative phosphorylation, the
major producer of free radicals. When the level of free radicals overwhelms the
cellular antioxidant defense system, a deleterious condition known as oxidative
stress occurs. ROS has an intimate relationship with mitochondrial function and
oxidative stress is believed to result from mitochondrial dysfunction. This
review highlights the role of oxidative stress and mitochondrial dysfunction as
key players in the neurodevelopmental pathophysiology. The mechanisms
associating these two disease states can lead to neuronal death,
neuroinflammation and impairment of energy metabolism. Biomarkers related to
both aspects will be highlighted to demonstrate their importance in the early
diagnosis of neurodevelopmental disorders like autism, cerebral palsy and
others. Treatments trials for oxidative stress or mitochondrial dysfunction
using nutritional supplements and antioxidants are reviewed in order to shed
light on recent strategies for the early intervention for neurodevelopmental
disorders.
