ALS and water bucket

Mao Zedong - (1893-1976) Chinese military and political leader, who led the Communist Party of China (CPC) to victory against the Kuomintang (KMT) in the Chinese Civil War, and was the leader of the People's Republic of China (PRC) from its establishment in 1949 until his death in 1976. Regarded as one of the most important figures in modern world history, Mao is still a controversial figure today, over thirty years after his death. He died of amyotrophic lateral sclerosis, commonly known in the U.S as Lou Gehrig's Disease and elsewhere as Motor Neurone Disease. Mao had been in poor health for several years and had declined visibly for some months prior to his death. - See more at: http://www.disabled-world.com/artman/publish/famous-als.shtml#sthash.theHt0dn.dpuf

Mao Zedong - (1893-1976) Chinese military and political leader, who led the Communist Party of China (CPC) to victory against the Kuomintang (KMT) in the Chinese Civil War, and was the leader of the People's Republic of China (PRC) from its establishment in 1949 until his death in 1976. Regarded as one of the most important figures in modern world history, Mao is still a controversial figure today, over thirty years after his death. He died of amyotrophic lateral sclerosis, commonly known in the U.S as Lou Gehrig's Disease and elsewhere as Motor Neurone Disease. Mao had been in poor health for several years and had declined visibly for some months prior to his death. - See more at: http://www.disabled-world.com/artman/publish/famous-als.shtml#sthash.theHt0dn.dpuf

 Mao Zedong - (1893-1976) Chinese military and political leader, who led the Communist Party of China (CPC) to victory against the Kuomintang (KMT) in the Chinese Civil War, and was the leader of the People's Republic of China (PRC) from its establishment in 1949 until his death in 1976. Regarded as one of the most important figures in modern world history, Mao is still a controversial figure today, over thirty years after his death. He died of amyotrophic lateral sclerosis, commonly known in the U.S as Lou Gehrig's Disease and elsewhere as Motor Neurone Disease. Mao had been in poor health for several years and had declined visibly for some months prior to his death. - See more at: http://www.disabled-world.com/artman/publish/famous-als.shtml#sthash.theHt0dn.dpuf

Mao Zedong - (1893-1976) Chinese military and political leader, who led the Communist Party of China (CPC) to victory against the Kuomintang (KMT) in the Chinese Civil War, and was the leader of the People's Republic of China (PRC) from its establishment in 1949 until his death in 1976. Regarded as one of the most important figures in modern world history, Mao is still a controversial figure today, over thirty years after his death. He died of amyotrophic lateral sclerosis, commonly known in the U.S as Lou Gehrig's Disease and elsewhere as Motor Neurone Disease. Mao had been in poor health for several years and had declined visibly for some months prior to his death. - See more at: http://www.disabled-world.com/artman/publish/famous-als.shtml#sthash.theHt0dn.dpuf

 已知ALS是由蛋白在上，下运动神经元堆积引起，就是说蛋白质降解途径出了问题。蛋白质降解
有三条途径，最常见的ubiquitin途径已经证实于此有关。2011的nature 文章说ubiquilin2
(ubiquitin-like protein)可引起染色体X显性遗传的 ALS/dementia(后者是一种类型的
老年痴呆）。这个基因在染色体X上，因此由这个基因突变引起ALS女多于男。
此外，还有多个基因的突变和ALS有关，第一个被发现的基因是SOD1（占20%），是的，就是“大宝
天天见”的那个酶， 估计是突变使酶失效，造成自由基堆积，损伤了线粒体。跟中国人有关的一个
基因叫PFN1 （Profilin 1），突变只在中国人里发现。下面讲治疗。
基因病只能基因治疗，但是神经细胞的基因治疗也是很难的，因为成年人的神经细胞不分裂，更难
表达外源基因。未来儿童的基因治疗和成年人的干细胞治疗是科研方向。作为普通人预防，
1.多吃水果蔬菜，清除多余自由基。
2.远离杀虫剂，农药等化学环境因子。
3.有条件做一下以上几个突变的基因检查。
The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop protein-rich inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.[46] These inclusions often contain ubiquitin, and generally incorporate one of the ALS-associated proteins: SOD1, TAR DNA binding protein (TDP-43, or TARDBP), or FUS.

Cause of ALS is found, Northwestern team says

Breakthrough in Lou Gehrig's disease could lead to treatment

August 22, 2011|By William Mullen, Tribune reporter

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Researchers at Northwestern University say they have discovered a common cause behind the mysterious and deadly affliction of amyotrophic lateral sclerosis, or Lou Gehrig's disease, that could open the door to an effective treatment.
Dr. Teepu Siddique, a neuroscientist with Northwestern's Feinberg School of Medicine whose pioneering work on ALS over more than a quarter-century fueled the research team's work, said the key to the breakthrough is the discovery of an underlying disease process for all types of ALS.

The discovery provides an opening to finding treatments for ALS and could also pay dividends by showing the way to treatments for other, more common neurodegenerative diseases such as Alzheimer's, dementia and Parkinson's, Siddique said.
The Northwestern team identified the breakdown of cellular recycling systems in the neurons of the spinal cord and brain of ALS patients that results in the nervous system slowly losing its ability to carry brain signals to the body's muscular system.
Without those signals, patients gradually are deprived of the ability to move, talk, swallow and breathe.
"This is the first time we could connect (ALS) to a clear-cut biomedical mechanism," Siddique said. "It has really made the direction we have to take very clear and sharp. We can now test for drugs that would regulate this protein pathway or optimize it, so it functions as it should in a normal state."
The announcement of the breakthrough is in Monday's issue of the research journal Nature. The paper lists 23 contributing scientists, including the lead authors, Northwestern neurological researchers Han-Xiang Deng and Wenjie Chen, and Siddique as senior author.
ALS afflicts about 30,000 Americans. With no known treatment for the paralysis, 50 percent of all ALS patients die within three years.
It is particularly tragic because it often strikes people who are very physically active. In 1941, New York Yankee baseball superstar Lou Gehrig died at 37 of the disease that now carries his name.
Amelie Gubitz, a research program director at the National Institute of Neurological Disorders and Stroke, said the Northwestern research is a big step forward in efforts worldwide to conquer ALS.
"You need to understand at the cellular level what is going wrong," said Gubitz. "Then you can begin to design drugs.
"ALS is a complicated problem, and Dr. Siddique's research adds a big piece to the puzzle that gives us important new insights."
A variety of proteins perform different functions within cells, and Deng and Chen led research that discovered a key protein, ubiquilin2, in the ALS mystery.

Ubiquilin2 in spinal and brain system cells is supposed to repair or dispose of other proteins as they become damaged. The researchers discovered a breakdown of this function in ALS patients.
When Ubiquilin2 is unable to remove or repair damaged proteins, the damaged proteins begin to pile up in the cells, eventually blocking normal transmission of brain signals in the spinal cord and brain, leading to paralysis.
There are three forms of ALS: "familial," which is hereditary and passed through genes; nonhereditary, which is called "sporadic"; and ALS that targets the brain, called "ALS/dementia."
Siddique was part of a study that made a breakthrough in ALS in the early 1990s, discovering the "familial" gene that causes the disease within some families. That breakthrough came after he began an ongoing study 25 years ago of an East Coast family that has lost more than 20 members to ALS.
Joanne Saltzman, a 72-year-old member of that family, recalled last week how she first learned of ALS when she was a small girl and her father, a naval veteran, was dying of the disease. Her grandfather died of it, too, as did four of her father's seven brothers.
Subsequently, one of Saltzman's sisters and many of her cousins died from ALS. It killed her 51-year-old son last October, she said in a phone interview, and in February her 52-year-old niece died of it.
"I am so excited by their new findings," Saltzman said of the Northwestern study. "Dr. Siddique has been studying our family for 25 years, and it is so encouraging for our remaining family."
"I told Dr. Siddique's office, if I could cut off my arm and send it to them I would if it would help them in the research," she said. "I would do anything. It is so important to me to be able to find some kind of cure for this awful disease."