Targets in ALS: designing multidrug therapies
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- 作者：Maria Teresa Carrì ; Giuliano Grignaschi and Caterina Bendotti
- 刊名：Trends in Pharmacological Sciences
- 出版年：2006
- 出版时间：May 2006
- 年：2006
- 卷：27
- 期：5
- 页码：267-273
- 全文大小：140 K
文摘
Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu–Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia and muscles, and evolves through the action of converging toxic mechanisms. Transgenic rodents that express human mutant SOD1 and develop a progressive paralytic disease are widely used to screen potential therapeutics. Treatments that interfere with a specific event in the neurotoxic cascade have been reported to produce a modest increase in rodent lifespan. Multi-intervention approaches, including novel methods to intercept the damage and to deliver molecules to vulnerable cells, have recently been shown to be more effective. Thus, new avenues for promising therapeutic approaches can be derived from multidrug treatments and/or the delivery of growth factors by viral vectors, in combination with exercise and/or diet regimens.