Neurodegenerative disorders are a major health burden both in the United States and worldwide. These diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, all stem from the progressive loss of neurons in the brain. The specific causes of these diseases (with the exception of Huntington’s) are complex, and are influenced by genetic and environmental factors. It is estimated that 5 million Americans are living with Alzheimer’s disease, 1 million are living with Parkinson’s, and 30,000 with Huntington’s, with many more at risk. Given these facts, it’s no surprise that the National Institute of Health spends a significant portion of its budget funding research aimed at understanding and treating these terrifying diseases.
One common element found in each of these disorders is an accumulation of iron in the brain. However, these accumulations are not the cause of disease, but are a secondary effect that exacerbate each condition. A new paper, published in Brain Research Bulletin, shows that CBD can protect against the effects of iron accumulation in the brains of rats. This research sheds light on the potential use of CBD as a way to treat the symptoms associated with neurodegeneration.
This research was designed to investigate a particular pathway by which iron accumulation could be causing disease. Our cells, like our bodies, are separated into multiple smaller compartments, each of which has a unique function. One of these compartments is called the mitochondrion (MT). MTs are the major site of metabolism in our cells, acting as a “power plant” of sorts. Cell types with high energy demands, like neurons and muscle cells, require a lot of MTs. If there aren’t enough MTs, or if they are damaged, the cells will die. Many neurodegenerative diseases are linked to MT dysfunction; therefore, the authors of this paper chose to assess MT function in the brains of rats suffering iron poisoning, which mimics many of the symptoms of these diseases.
Rat brain MT health was assessed in a number of ways. First, they looked at damage to MT DNA. MTs, unlike the other “organs” of a cell, have their own genome that is separate from ours. Accumulated iron disrupts normal metabolism, generating chemicals which can damage MT DNA. If this damage is not repaired properly, sections of the DNA are deleted from the genome, potentially disrupting genes necessary for MT function. The authors found that DNA from the MTs of rats with iron poisoning had more deletions than DNA from healthy rat MTs. This suggests that iron accumulations attack the DNA of MTs in the brain. CBD treatment had no effect on the development of these deletions, but this is likely an affect of their methodology.
Next, they tested expression levels of two genes associated with iron metabolism in the MT. One is required for iron uptake by MTs, while the other is used for iron storage in the MT. Using two different methods, they showed that expression of the iron uptake gene is not affected by iron poisoning. However, the iron storage gene is affected. Interestingly, treatment with CBD increased this gene’s expression back to normal levels.
Finally, they assessed the activity of two metabolic genes that function in the MT. One of these genes is necessary for the MT’s function as a power source. Without it, the MT will cease to function, and the cell will die. They found that iron accumulation caused a severe reduction in this gene’s activity, but that treatment with CBD completely reversed this effect. The second gene was unaffected by the iron poisoning. These results show that CBD is having a protective effect against iron poisoning, restoring normal MT metabolism in these cells.
The results of this paper point to a potential mechanism by which CBD can ameliorate the effects of neurodegenerative diseases. The authors suggest that iron accumulations, which happen as a result of the onset of disease, cause an accumulation of deletions in the DNA of neuronal MTs, which in turn affects their ability to function, leading to cell death. CBD is able to restore expression of some genes required for MT iron metabolism, and restore metabolic functions. How it is able to perform this function is still an open question.
While these results are promising, this paper leaves a lot to be desired. For one thing, the authors only tested two sites in the MT genome for deletions, and used that data to draw conclusions about the entire MT genome. The same is also true of their examination of MT gene expression and metabolic function. Further, they make no effort to show whether or not CBD has an effect on clearing iron accumulations from the brain. It’s possible that the iron accumulations are still present, but CBD is combating their effects. Finally, how is CBD able to affect metabolism in MTs? Clearly, there is more work to be done to elucidate CBD’s mechanism of action.
Regardless, this new data points to CBD as a potential therapy for neurodegenerative diseases. While it won’t cure or reverse cognitive decline, it may slow the process and offer a better quality of life for those struggling with these conditions.