Neurodegenerative disorders

摘要

"Inow begin the journey that will lead me into the sunset of my life," was how Ronald Reagan described his remaining life. That was seven years ago when he told the world that he had Alzheimer's disease. The sunset has been a prolonged one, as is usual in most neurodegenerative disorders, of which Alzheimer's is a prototype. All have an insidious onset, progress slowly over years, and death is usually due to an intercurrent illness and not directly due to the disease itself. Predictably the global burden of diseases like Alzheimer's will rise with increasing longevity. Much of the burden is also borne by carers and relatives. Reagan's daughter, Maureen Reagan, summed up what the illness means to carers. "[Ronald's wife Nancy is] the one who wakes up with it every morning and goes to sleep with it every night" Unfortunately Nancy Reagan's burden does not figure in any report of global health. Neurological and psychiatric disorders taken together account for more chronic suffering than all other disorders combined. Neurodegenerative disorders have largely contributed to the neurologist's reputation for being accurate in diagnosing illnesses but hopeless at treating them. Research on prions, amyloid deposits, and β sheet breaker peptides may change all mat. The pathogenesis of many neurodegenerative disorders is now known to be associated with the accumulation of protein deposits within brain parenchyma. In these diseases a normal soluble cellular protein is converted into an abnormal insoluble aggregated protein rich in β sheets that is toxic-for example, β amyloid in Alzheimer's disease. Many neurodegen-erative disorders are associated with amyloid formation. Even those that are not (for example, Hunting-ton's disease and spinocerebellar ataxias) are associated with CAG repeats that may cause proteins to aggregate and form toxic inclusion bodies. Compounds which will interfere with p sheet protein formation hold therapeutic promise, and recently designed agents like β sheet breaker peptides are being tried out in animal experiments. Another therapeutic strategy uses the immunological approach. In-transgenic mice that have neuropathology related to Alzheimer's disease, immunisation with amyloid β antigen reduces or prevents amyloid deposits.