Oncoding RNA may Promote Alzheimer's Disease: Boffins

Scientists have pinpointed a small RNA that spurs cells to manufacture a particular splice variant of a key neuronal protein, potentially promoting Alzheimer's disease (AD) or other

Scientists have pinpointed a small RNA that spurs cells to manufacture a particular splice variant of a key neuronal protein, potentially promoting Alzheimer's disease (AD) or other types of neurodegeneration.

Although scientists have identified numerous proteins and RNAs that influence alternative splicing, they haven't deciphered how cells fine-tune the process to produce specific protein versions.

Arrowing in on Alzheimer's Disease
Recently the number of genes known to be associated with Alzheimer's disease has increased from four to eight, including the MS4A gene cluster on chromosome 11.

Four years ago, researchers identified a set of 30 small, noncoding RNAs that they suspected help regulate gene expression.

Italian researchers have now determined the function of one of the RNA snippets, known as 38A, which hails from a noncoding part of the gene that encodes the protein KCNIP4.

KCNIP4 helps ensure that neurons fire impulses in a characteristic slow, repeating pattern.

Research Finds That Alzheimer's Cure May Lie in Recycling Proteins
For years, scientists and doctors have believed that protein aggregates called amyloid fibrils found in the brain were the culprit behind Alzheimer's disease.

The researchers found that 38A spurs cells to produce an alternative splice variant of KCNIP4, Var IV, which disrupts this current, potentially leading to neurodegeneration.

KCNIP4 normally interacts with gamma-secretase, the enzyme complex that helps generate beta-amyloid (Abeta), a protein that accumulates in the brains of AD patients.

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The Feinstein Institute for Medical Research scientists have discovered that a molecule c-Abl, which has a known role in leukaemia, also has a hand in Alzheimer's disease.

But Var IV can't make the connection, possibly disturbing Abeta processing.

Supporting that notion, the researchers found that levels of 38A were more than 10 times higher in brain cells from AD patients than in controls and that 38A hiked output of the more dangerous Abeta isoform Abeta 1-42.

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People who are stressed are at increased risk of developing Alzheimer's disease, according to a study.

The study appears in the May 30 issue of The Journal of Cell Biology.

Source-ANI