Figure 5.

Agrin as a potential serum biomarker of skeletal muscle aging. Shown is the linkage between the disintegration of the neuromuscular junction during skeletal muscle aging and resulting preferential loss of neurotransmission to fast type II fibers. A potential biomarker candidate of this process is the release of carboxy-terminal agrin fragments (CAF) that can be measured in the serum (sCAF) of patients suffering from sarcopenia of old age. At the neuromuscular junction, the proteoglycan agrin associates with the dystroglycan complex (alpha/beta-DG), which forms an integral part of the sub-sarcolemmal utrophin/dystrophin lattice and its associated proteins (DAPs) at the post-synaptic membrane. During skeletal muscle aging, the integrity of the neuromuscular junction is lost, and agrin is proteolytically cleaved by the enzyme neuro-trypsin. This results in the production of distinct agrin fragments that can be conveniently detected in a minimally invasive way in suitable biofluids.