小鼠模型,ALS z-bo 2020-11-30 410

　　With the popular Ice Bucket Challenge this summer, gradual freezing syndrome (ALS, amyotrophic lateral sclerosis) has attracted widespread public attention. "Gradual freezing disease" is one of the five terminal diseases listed by the World Health Organization. The medical name (Amyotrophic Lateral Sclerosis, "ALS") is a type of Motor Neuron Disease (MND). Motor nerve cells in the brain, brainstem and spinal cord are invaded, and the patient's muscles gradually atrophy and become weak, and even paralyzed. The body seems to be frozen gradually, so it is commonly known as "gradually frozen person." Since the sensory nerves are not violated, this disease does not affect the patient's intelligence, memory and sensation.

　　Ubiquinone protein 2 encoding gene (UBQLN2) mutations can cause ALS and ALS/dementia. However, the molecular mechanism is still unknown. ALS/dementia is a form of ALS and can also damage the brain. At present, scientists at Northwestern University Feinberg School of Medicine have developed an animal model of ALS/dementia for the first time. This development will allow researchers to directly observe the brains of live mice under anesthesia at the microscopic level. Allows researchers to directly monitor test drugs to determine whether they work.

　　Northwestern University scientist and senior author Dr. Teepu Siddique said: "This new model will allow real-time rapid detection and direct monitoring of drugs. This will allow scientists to take quick action to accelerate drug therapy trials."

　　The new mouse model has the pathological characteristics of human diseases and carries mutations in the UBQLN2 (ubliqulin 2) and SQSTM1 (P62) genes (discovered by Siddique and colleagues in 2011). Pathology is related to various forms of ALS and ALS/dementia.

　　Dr. Siddique and Han-Xiang Deng, co-corresponding authors of this article, stated that they have replicated the behavioral, neurophysiological and pathological changes in ALS-related dementia in mice. Siddique is a professor of neurology at Northwestern University Feinberg School of Medicine and a neurologist at Northwestern Memorial Hospital. Deng is a professor of neurology at Feinberg School of Medicine. They published this research in the journal PNAS on September 22, 2014.

　　Siddique said that it has always been difficult for scientists to replicate ALS genetic mutations, especially in animal models, which hinders the progress of drug treatment trials.

　　5% or more of ALS cases have ALS/dementia. Siddique said: "Compared to ALS alone, ALS with dementia is a more malignant disease because it attacks the brain, causing changes in behavior, language, and paralysis."

　　ALS affects approximately 350,000 people worldwide, with an average survival period of only three years. In this progressive neurological disease, the degeneration of neurons can cause muscle weakness, impaired speech, swallowing, and breathing, and ultimately lead to paralysis and death. Related dementia affects behavior and may affect decision-making, judgment, insight, and language.