Iron plays an important role in normal human functioning. It is involved in oxygen transport, electron transport and many metabolic processes. Iron in the body is bound in proteins to prevent excess toxicity. Brain cells like oligodendrocytes, neurons and microglia all express ferritin, an iron storage protein.
Despite the importance of iron to normal human functioning, excessive accumulation of iron in the brain has many negative consequences. Increased iron can damage cells directly or perturb the cellular environment. Iron accumulation can make cells more vulnerable to toxins, inflammation or apoptosis. Additionally, high iron levels contribute to reactive oxygen species generation and protein aggregation, which lead to damaging oxidative stress.
For individuals with Huntington's disease, increased iron levels have primarily been observed in the basal ganglia. The basal ganglia is a brain region that includes the striatum, internal and external globus pallidus, subthalamic nucleus and substantia nigra. One study using magnetic resonance imaging to quantify iron levels in HD patients found the most noticeable iron accumulation in the striatum and the globus pallidus. For more information about the basal ganglia click here or visit the HOPES Brain Tutorial here.
Iron levels increase early in the disease process and continue to increase with advancing age. The steady accumulation of iron in HD patients suggests that it may play a role in the progression of the disease.
Iron is important for the normal function of neurons and many areas of the brain naturally have high iron content. However, abnormal amounts of iron specifically in the basal ganglia, is a hallmark of neurodegenerative disorders. It has been observed in Parkinson's disease, Alzheimer's disease and Friedreich's ataxia as well as in HD. Although these other neurodegenerative diseases share with HD problems of iron regulation in the basal ganglia, those problems do not manifest identically. For instance, Parkinson's disease is characterized by iron accumulation in the substantia nigra, which has not been observed in HD.
There are several reasons why iron might accumulate in the course of a neurodegenerative disorder. The iron accumulation might be a direct result of the disease. In the case of HD, scientists do not yet understand why this would occur. But it is also possible that the iron accumulation is a consequence of secondary effects of the disease. For instance, in HD iron accumulation might occur because after neuronal loss (a direct result of HD) the cells that died are replaced by cells with higher iron content (secondary effect). Another alternative is that iron accumulation is facilitated by the breakdown of the blood brain barrier, an event which might allow excess iron from the body to enter the brain.
Last Modified: 05/22/2009
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