Recycling System Overload
Implicated in IBM

Overloading of a normal cellular process called autophagy (self-digestion) is likely to be part of the problem in inclusion-body myositis (IBM), say Christian Munz at Rockefeller University in New York and colleagues.

IBM, a disease involving both inflammation and degeneration of muscle, can be inherited (familial) but is usually sporadic (nonfamilial).

Researchers have long debated whether the primary cause of IBM is a misguided attack on muscle tissue launched by the immune system, with degeneration of muscle cells occurring as a result; or a degeneration of muscle cells, with inflammation resulting from the immune system's attempt to contain the damage.

In findings published in the May issue of Annals of Neurology, Munz and colleagues report that beta-amyloid, an abnormally folded protein found in excess in IBM-affected muscle cells, is targeted to the autophagy pathway for its degradation.

The job of this pathway is to break down and recycle old and defective protein molecules, and it appears to be particularly important for protein turnover and quality control in skeletal muscle tissue.

The investigators speculate that, in patients with sporadic IBM, the autophagy system is overwhelmed and not up to its job, resulting in a buildup of abnormal and potentially toxic proteins.

In a report published in the same issue of Annals of Neurology, viral infection is implicated as the initial cause of an attack by the immune system on muscle fibers in at least some cases of IBM. (Marinos Dalakas at the National Institutes of Health is an author on both reports.)

"Our data indicate that the autophagic pathway is involved in beta-amyloid-associated degeneration in sporadic IBM muscle and suggest that harnessing the autophagy pathway could have therapeutic merit," Munz and colleagues write.

"However, in addition to its central role in preventing intracellular protein accumulation, induction of autophagy has been associated with various forms of cell death. In exploring the therapeutic potential of autophagy in diseases associated with accumulation of ... proteins, it will be essential to better define the signaling pathways either leading to protective autophagy or autophagic cell death."