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Biological Chemistry

Progress For ALS Research

Affected motor neurons generated from stem cells allow drug screening, disease study

by Elizabeth K. Wilson
August 6, 2012 | APPEARED IN VOLUME 90, ISSUE 32

A natural product from cashew plants reduces abnormalities in motor neurons affected by the devastating neurodegenerative disease amyotrophic lateral sclerosis (ALS), a multi-institute team from Japan reports (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3004052). Scientists have not had good drug evaluation models, nor samples of motor neurons from ALS patients, with which to study the pathology of, or explore possible drug candidates for, this disease. Now, the group, led by Haru­hisa Inoue at Kyoto University, has taken skin cells from ALS patients, converted them into stem cells, and generated motor neurons from them. These motor neurons carried hallmark abnormalities associated with ALS, including excess amounts of a mutant protein called TDP-43. With a ready source of diseased motor neurons in hand, the group tested the effects of four compounds on the cells. In particular, they found that one of many so-called anacardic acids isolated from cashew nut shells, a compound known to be a histone acetyltransferase inhibitor, reversed some of the effects of ALS. For example, it reduced the neuron’s expression of TDP-43. This work could provide a new platform from which to study the disease and screen for potential drug treatments, the authors note.

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