Abstract:
:Down's syndrome (DS) or trisomy 21 is the most common genetic cause of mental retardation. Development of the DS brain is associated with decreased neuronal number and abnormal neuronal differentiation, and adults with DS develop Alzheimer's disease. The cause of the neurodegenerative process in DS is unknown. Here we report that cortical neurons from fetal DS and age-matched normal brain differentiate normally in culture, but DS neurons subsequently degenerate and undergo apoptosis whereas normal neurons remain viable. Degeneration of DS neurons is prevented by treatment with free-radical scavengers or catalase. Furthermore, DS neurons exhibit a three- to fourfold increase in intracellular reactive oxygen species and elevated levels of lipid peroxidation that precede neuronal death. These results suggest that DS neurons have a defect in the metabolism of reactive oxygen species that causes neuronal apoptosis. This defect may contribute to mental retardation early in life and predispose to Alzheimer's disease in adults.
journal_name
Naturejournal_title
Natureauthors
Busciglio J,Yankner BAdoi
10.1038/378776a0subject
Has Abstractpub_date
1995-12-21 00:00:00pages
776-9issue
6559eissn
0028-0836issn
1476-4687journal_volume
378pub_type
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