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A noncoding RNA may drive Alzheimer’s disease

Nature Medicine

June 30, 2008

Scientists have found a molecular mechanism that may drive the progression of Alzheimer’s disease. The mechanism, involving the enzyme Beta secretase 1 (BACE1), is described online in Nature Medicine this week, and could become a target for future therapeutic efforts.

Many protein-coding RNAs have natural complementary partners, most of which seem to be noncoding RNAs. Claes Wahlestedt and colleagues have identified a noncoding complementary partner for the enzyme BACE1, which positively regulates the levels of BACE1 RNA and protein, and is present in people with Alzheimer’s disease and in a mouse model with similar symptoms.

Upon exposure to amyloid-beta, the molecule that results from the activity of BACE1 and that accumulates in the amyloid plaques characteristic of Alzheimer’s disease, expression of the noncoding RNA is enhanced, which increases the levels of BACE1 and generates additional amyloid-beta through a positive feedback loop.

doi: 10.1038/nm1784 | Original article

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