Iron likely plays causative role in Parkinson's and Multiple System Atrophy
In research conducted by the National Institute of Child Health and Human Development (NICHD) to be published in the February 2000 issue of the journal Nature Genetics, the discovery was made that genetically engineered mice lacking the gene for iron regulatory protein 2 develop iron deposits in the brain and Parkinson's disease symptoms. Iron regulatory protein 2, or IRP2, regulates how much iron is in the cell by governing the actions of other proteins involved in iron metabolism, protecting the cell from iron overload. IRP2 is found most abundantly in the brain. Mice engineered to lack this protein developed normally, but later developed difficulty with walking and movement similar to that found in humans with Parkinson's disease and the disease Multiple System Atrophy, also known as Parkinson's Plus. The mice were found to have iron deposits in the cerebellum and basal ganglia of their brains, areas of the brain involved in movement and the same areas as those in the human brain affected by Multiple System Atrophy. Excess iron in the brain has been observed with Parkinson's disease as well, but the areas of the brain affected are different, which leads researchers to believe that although IRP2 is not involved in Parkinson's, other genes involved in iron metabolism could be implicated in the disease.
NICHD Director Duane Alexander MD, stated, "Researchers have long debated whether the characteristic iron deposits of these diseases are the cause or the result of the disease process. This is a strong clue that iron may play a causative role in Parkinson's and similar disorders."
Senior Investigator Tracy A Rouault, MD is seeking Multiple System Atrophy patients for participation in a study to test for IRP2 defects. Those with Parkinson's symptoms are also encouraged to participate because Parkinson's disease can be mistaken for Multiple System Atrophy. Prospective participants' physicians may contact Dr. Rouault at Rouault@mail.nih.gov
Vitamin E improves immune function, reduces oxidative stress in humans
December 2000's Journal of Nutrition was the site of a report detailing the effects of vitamin E on oxidation and immune function in an Asian population. Although studied in animals, elderly humans and in vitro, vitamin E's effect on immune cell subsets has not been well characterized in a young, healthy adult population. Immune system cells produce free radicals in order to destroy invading organisms, but the immune system itself is damaged by oxidants such as oxygen free radicals, diminishing its response.
Hormonal link found between diabetes and obesity
The long-sought connection between diabetes and obesity appears to have been discovered by researchers in a series of experiments conducted at the University of Pennsylvania School of Medicine. Obesity affects over 80% of people with type 2 diabetes, the form of the disease characterized by resistance to insulin. Increased storage of fat molecules in adipose tissue causes insulin resistance, but until now, its ability to cause the same in other tissues such as the muscles and liver remained unknown.
Longterm vitamin C intake not a strong factor in iron absorption
Studies have shown that vitamin C taken with a single meal containing iron greatly enhanced iron absorption. Although this may be of benefit for some populations, life extensionists have avoided excessive iron because of the correlation between high iron levels and heart disease, cancer and Parkinson's disease. Thankfully, other research has shown that prolonged supplementation with vitamin C has a negligible effect on iron absorption. In one study, two grams of vitamin C supplemented for one year did not increase iron stores. A study published in January 2001's American Journal of Clinical Nutrition confirms that finding and presents evidence that vitamin C's ability to enhance iron absorption may be valid only in the setting of a single meal preceded by fasting used in clinical studies.
In an article published in recent issue of Hammersmith Research, researchers from the Hammersmith Hospital and Imperial College School of Medicine in London reported the successful engineering of immune cells that seek out and destroy leukemia cells. Over six years of research has identified the overexpression a single gene, WT-1, in cells that cause leukaemia. The identification of this gene enabled the researchers to develop immune cells that recognize the WT-1 on cancerous cells and destroy them, while ignoring normal cells of the same type. The research was originally published in the April 1 2000 issue of the journal, Blood.
Further evidence linking homocysteine and dementia
A letter published in the January 2001 issue of American Journal of Clinical Nutrition, provided more evidence of a correlation between elevated homocysteine levels and dementia. Hyperhomocysteinemia has been recently identified as a risk factor for atherosclerosis and Alzheimer's disease, and folic acid, vitamin B6 and B12 have been recommended to lower homocysteine levels. An Austrian study of thirty-one patients with cognitive decline found an elevation of homocysteine compared to controls and in some patients other vascular disease risk factors were noted. An inverse correlation was found between test scores that measured cognitive skills and serum homocysteine levels, as well as between folic acid and homocysteine levels. Higher folic acid levels were associated with better test scores.
When nine of the patients were treated with 50 mg vitamin B1, 50 mg vitamin B6, 5 mg folic acid and 50 micrograms vitamin B12, all of the patients experienced a lowering of homocysteine to normal levels.
This study confirms several others that have shown a link between B vitamin status, homocysteine and brain function. Authors of other studies have mentioned that these vitamins are often deficient in elderly populatoins, and that deficiencies can result in brain ischemia, through occlusive vascular disease, stroke or blood clots. The author of this study pointed out that vascular disease risk factors such as hypertension have been recognized in Alzheimer's disease. It is also interesting to note that nonsteroidal antiinflammatories have been shown to be helpful in preventing both vascular disease and Alzheimer's disease. The authors of this study conclude that vascular disease risk factors may contribute to the pathophysiology of Alzheimer's disease.
New Alzheimer's target found
In yet another exciting recent discovery in the field of Alzheimer's disease, Gladstone Institute of Neurological Disease and University of California San Francisco researchers have found that a protein called alpha1-antichymotrypsin or ACT, a serine protease inhibitor that prevents protease enzymes from digesting proteins, can significantly increase the amount of amyloid plaque in the brains of mice. It had been known that Alzheimer's patients have increased production of ACT, which is found in the amyloid plaques characteristic of this disease, but researchers were unaware of whether the presence of ACT combatted or enhanced the buildup of these plaques. It has recently been discovered that the plaques are most likely the cause of Alzheimer's disease symptoms (see What's Hot, Jan 3, 2001).
Mechanism of action found for aspirin in cancer cell apoptosis
The November/December 2000 issue of the journal Neoplasia published a research article which explained the discovery of how aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptotic cell death in cancer, a process that had heretofore been unknown. It has been believed that aspirin and other NSAIDs exerted their known colon cancer preventive effects by inhibiting cyclooxygenase (COX) activity, but recently researchers have proposed that NSAIDs' anticancer ability lies in their induction of apoptosis, the process whereby programmed cell death occurs. There are several possible pathways by which apoptosis ocurs. The researchers studied a cultured cancer cell line and found that aspirin acts via a pathway which involves the release of cytochrome c from the mitochondria of the cell to bind with Apaf-1 or apoptotic protease activating factor. This complex activates caspase proteases, enzymes that cause cellular destruction. Cells lacking Apaf-1 proved to be resistant to apoptosis stimulated by aspirin, as were cells that overexpressed the antiapoptotic protein Bcl-2, known to prevent the release of cytochrome c.
Melatonin may protect against Parkinson's disease
The theory that Parkinson's disease has an environmental cause has recently gained credence. A study published in the December 2000 issue of the journal Nature Neuroscience demonstrated that the pesticide Rotenone caused Parkinson's symptoms when administered to rats. The article indicated that Rotenone may cause the mitochondria, which are the power plants of the cells, to produce free radicals, thereby causing the damage that leads to Parkinson's disease.
Human proteome database completed
Another genetic landmark was passed on January 4 when it was announced by Large Scale Biology Corporation (LSBC) that it had completed the initial version of its proprietary human proteome database, the Human Protein Index(tm) version 1.0, or HPI v1.0. The database provides a complete inventory of all human proteins A summary of the research will be published in the January 18 2001 issue of the journal Proteomics.
Robert Erwin, CEO of Large Scale Biology Corporation commented, "With the completion of the HPI v1.0, we now have a comprehensive process for analyzing the proteins encoded by human genes. Diseases are caused by changes in proteins that are not always predictable by gene analysis alone, and we believe HPI v1.0 provides an important new baseline for determining the roles of both genes and proteins in health and disease. We expect the protein discoveries for medical applications enabled by HPI v1.0 to drive a major shift in pharmaceutical research and development from genes to proteins . . . "
Leigh Anderson, President of LSBC's proteomics subsidiary stated, "The HPI v1.0 gives us a first look at the protein components of all the major tissues of the human body. Our initial analysis of the HPI has turned up new candidate diagnostic markers of tissue damage, as well as fascinating insights into the differences between tissues, for example, in different regions of the brain. We believe that over the long term, the HPI provides a unique foundation for our ongoing investigations of specific diseases."
Long-sought stroke prevention in diabetes with ramipril
The January 2 2001 issue of American Heart Association (AHA) journal Circulation and the January issue of AHA's Stroke published a comprehensive article entitled "Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association" which, among other important guidelines, recommended the use of the drug ramipril, or Altace R to diabetics to prevent stroke. These latest recommendations are based on the findings of the HOPE Trial, which stands for Heart Outcomes Prevention Evaluation which showed that diabetics taking the drug can reduce the risk of stroke by a third. The findings of the HOPE trial were published in the January 20, 2000 issue of the New England Journal of Medicine.
Dr Probstfield also noted that, "The incidence of diabetes greatly increases with age. More than one in six Americans age 65 and over has diabetes. Because the risk of cardiovascular disease also increases with age, the threat of cardiovascular disease should be a particular concern for older adults with diabetes."
Alzheimer's plaques probable cause, not effect
The Journal of Neuroscience (volume 21, 2001) published a report of research conducted by the National Institute of Environmental Health Sciences (NIEHS) that the plaques found in the brains of Alzheimer's patients disrupt brain signals which may contribute to the memory loss experienced by this group. These plaques contain a protein called beta-amyloid and their presence is confirmative of an Alzheimer's diagnosis upon autopsy of the brain. The beta-amyloid peptide has been found in the brains of both humans and animals. Although it had been frequently speculated, it had not been known whether these plaques were causative of the disease's symptoms.