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hi all some more interesting news with very interesting potential janet > ---------------------------------------------------------------------- > Cell structures may be key to diseases > ---------------------------------------------------------------------- > > Copyright 1997 Nando.net > Copyright 1997 Pittsburgh Post-Gazette > > (Mar 18, 1997 01:02 a.m. EST) -- After years of studying the care and > feeding of brain cells, Ian Reynolds can boil down his advice for > maintaining a healthy brain to just five words: Be nice to your > mitochondria. > > In a popular culture where mitochondria come up in conversation about > as often as a politician turns down a campaign contribution, it's not > likely to challenge "Show me the money" as a catch phrase. > > But neuroscientists such as Reynolds increasingly suspect that the > mitochondria inside nerve cells may prove important in the treatment > of strokes, brain trauma and such neurodegenerative diseases as > Parkinson's disease, Alzheimer's disease and Huntington's disease. > > Mitochondria are structures within each cell that produce adenosine > triphosphate, or ATP, a fuel source that keeps the rest of the cell > running. It is the failure of these tiny mitochondria that seem to > result in the death of brain cells that underlie all of those > diseases. > > Reynolds, a pharmacologist at the University of Pittsburgh Medical > Center, last September reported in the Journal of Neuroscience that he > had found a portion of the mitochondrion that only functions when it > is about to die. > > "We've called this thing a suicide mechanism," said the London-born > Reynolds, a beefy 37-year-old who has been at Pitt since 1988. > > If a drug can be found that kept that mechanism from working, doctors > might be able to preserve more brain cells -- and thus brain function > -- following a stroke or brain injury and perhaps slow the progression > of diseases such as Parkinson's and Alzheimer's. > > "People are jumping all over it," Reynolds said of the discovery, > noting five related research papers have since been published. > > "The evidence is not absolutely conclusive," cautioned Dr. Steven > Rothman, a neurologist at Washington University in St. Louis. But > mitochondrial changes may well turn out to be a key to new treatments > for some brain injuries and diseases. > > For instance, cyclosporine, a drug widely used to prevent organ > rejection following transplantation, appears to block the mechanism > Reynolds described, Rothman said. The combination of the suicide > mechanism and possible methods of blocking it has made this an > extremely active area of research, he added. > > It all adds to science's understanding of cell death that has > developed rapidly since the 1980s. > > Brain cells, called neurons, can be killed rapidly by cutting off > their supply of blood and oxygen, as occurs during a stroke or brain > trauma. Aside from rapidly restoring blood flow, little can be done to > save those cells. But scientists know that these injuries also can > trigger processes in the brain that lead to the death of neurons not > immediately affected by the injury. > > It was research by Rothman and other researchers during the 1980s that > established that these neurons were somehow being poisoned by > neurotransmitters -- the very chemicals the brain uses to pass > messages between cells. Further work by researchers such as Dr. Roger > Simon at the Insitute of Psychiatry in London, now chief of neurology > at Pitt, showed that the guilty neurotransmitter was glutamate. > > Glutamate accounts for about 70 percent of the "excitatory" signals > transmitted in the brain, Reynolds said. When brain cells die, they > release massive amounts of glutamate. The released glutamate is picked > up by other, still healthy cells. The glutamate overwhelms these > cells, however, overstimulating them and causing them to die. > > Neuroscientists have thus concluded that blocking the effects of > glutamate might prove an effective treatment for stroke and trauma; > indeed, a number of glutamate blockers or antagonists already are > being tested in local hospitals on stroke patients. In the case of > brain trauma, however, research by Pitt's Dr. Donald Marion has shown > that cooling the body for a day or two can be as effective if not more > effective than these experimental drugs. > > One problem with glutamate-inhibiting drugs is that they block not > only the unwanted glutamate but all glutamate, including that used in > normal brain functioning, Reynolds said. That can cause unwanted side > effects, such as hallucinations. > > A better class of drug would block only a chemical or process not > involved in normal brain function, he noted. The search for such a > mechanism has drawn Reynolds and his colleagues ever deeper into the > workings of the cell. > > Glutamate, they know, causes calcium to enter the cell, leading to > cell death. And calcium, it seems, makes a bee line to the > mitochondria. > > The mitochondria convert glucose into ATP, which serves as an energy > source for the rest of the cell. The calcium signals the mitochondria > to speed up production of ATP. > > But too much calcium eventually upsets the balance of enzymes and > electrical charges necessary to produce ATP. Production slows to the > point that the mitochondria begin consuming ATP. > > "That's the start of the end for the cell," Reynolds said. At this > point, his laboratory studies of neurons have shown that something > called the permeability transition pore opens in the mitochondrion's > outer membrane, shutting down its operation. As the mitochondria die, > the cell loses the power to sustain itself and it too dies. > > "The only time when we know this 'pore' is turned on is cases when > the neuron is going to die," Reynolds said. "What we need, > unquestionably, are drugs to block that thing. > > In the case of brain trauma or stroke, a drug that blocked the > permeability transition pore might keep some cells from dying until > blood flow was restored and brain chemistry settled down to normal > within a matter of hours or days, Reynolds said. > > In degenerative diseases, such as Alzheimer's or Parkinson's, neurons > die over a period of years. Each disease is caused by a slightly > different mechanism, but in each the net effect is to make neurons a > bit more fragile, so that they are more vulnerable to injuries, or > changes in oxygen and nourishment that would not affect a healthy > cell. In these cases, a drug that blocked the permeability transition > pore might make these cells a bit more resilient to these upsets, > slowing the progression of the disease. > > Though cyclosporine can block the pore, the dosages required are too > high to be practical, Reynolds said, so another drug will have to be > discovered or invented before treatment is a reality. And whether such > a drug would make a difference in clinical use is a matter of > speculation, he acknowledged. > > "It's a theory that's based on reality," Reynolds said. "But we may be > able to be bold because we're ignorant." > > http://www.nando.net/newsroom/ntn/health/031897/health31_19245.html [log in to unmask]