( An enzyme involved in the formation of ...)Alzheimers Disease Enzyme may Interfere With Brain Function,Health

An enzyme involved in the formation of the amyloid-beta protein associated with Alzheimers disease can also alter the mechanism by which signals are transmitted between brain cells , the disruption of which can cause seizures.

These findings from researchers at the MassGeneral Institute for Neurodegenerative Disorders may explain the increased incidence of seizures in Alzheimers patients and suggest that potential treatments that block this enzyme called beta-secretase may alleviate their occurrence.

Alzheimer's disease is characterized by plaques within the brain of the toxic amyloid-beta protein. Amyloid-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes BACE and gamma-secretase which releases the amyloid-beta fragment.

Signaling impulses in nerve cells are transmitted via voltage-gated sodium channels, structures on the cell membrane that transmit electrochemical signal by admitting charged sodium particles into the cells interior. Sodium channels consist of an alpha subunit, which makes up the body of the channel, and one or two beta subunits that help to regulate the channels activity.

Previous studies from Kovacs team and others showed that the BACE and gamma-secretase enzymes that release amyloid-beta from APP also act on the beta2 subunit of neuronal sodium channels. The current study was designed to examine how this processing of the beta2 subunit may alter neuronal function.

Lead author Doo Yeon Kim, PhD, and colleagues first confirmed that the beta2 subunit, similar to APP, can be acted on by BACE and gamma-secretase, releasing a portion of the beta2 molecule from the cell membrane.

A series of experiments using brain tissue from animal models and from Alzheimers patients revealed the following series of cellular events: Elevated levels of the free beta2 segment within the cell appear to increase production of the alpha subunits, but
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