ALS tagged posts

Neurons, red, created from ALS patients bearing the C9orf72 mutation, show clumps of the RanGAP protein, yellow, in their nuclei, white. The nuclei of other cells are in blue.
Credit: Jeffrey Rothstein laboratory, Johns Hopkins Medicine

The 1st steps in how a common gene mutation causes brain damage associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been found by Johns Hopkins researchers. Altered C9orf72 gene on human chromosome 9, causes RNA molecules to block critical pathways for protein transport, causing a molecular traffic jam outside brain cell nuclei and affecting their operations and survival. In a proof-of-concept experiment, a molecular therapy eased the jam and restored molecular flow into the cell’s core.

The mutation, the most comm...

It could lead to the development of new drugs to treat the disease. The study found that the protein fragment, sAPPα, inhibits the proteolytic enzyme BACE1. Increased BACE1 activity contributes to production of the amyloid beta aggregates and plaques that are the hallmark of Alzheimer’s.

“Because sAPPα inhibits the BACE1 enzyme, it may be possible that it can be used to help prevent potentially dangerous increases in BACE1 activity, and thus prevent the onset of Alzheimer’s disease,” A/Prof Varghese John.

The protein fragment sAPPa is normally produced by neurons and is involved in maintenance of memory...