Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, is a disease in which the motor neurons die off, resulting in a gradual loss of muscle power and eventually paralysis. The most famous patient is without doubt Stephen Hawking, although the disease has progressed in him in a very atypical way. Most patients die within three to four years after the first symptoms, caused by the paralysis of the muscles involved in breathing.
About 5-10% of cases are inherited, but most happen spontaneously. Incredibly, about 20 different defective genes can cause this disease, and the most common defective gene is C9ORF72. This gene contains a variable number of copies of a short repetitive sequence, called a repeat. Healthy people have 23 or fewer repeats while people with ALS can carry hundreds or even thousands of copies. Another interesting fact is that this mutation, unlike other causes of ALS, is associated with a type of dementia called frontotemporal dementia.
In three new studies published in the journals Nature and Nature Neuroscience the mechanism by which these extra repeats cause the neurodegeneration in ALS has been uncovered. Our genome is located in a membrane enclosed space, the nucleus. Communication between the nucleus and the rest of the cell happens through little pores in the membrane of the nucleus. All three studies uncovered that the transport of molecules through the nuclear pores was impaired but they differ on the exact culprit that blocks these pores. Interestingly, nuclear pores have been found to be damaged during normal aging and so the findings from these ALS studies might also be applicable to other neurodegenerative diseases.
Read more at Science Mag