Somatostatin in Alzheimer's disease: A new Role for an Old Player.

ABSTRACT: The amyloid beta (A?) peptide is central to the pathogenesis of Alzheimer's disease (AD). Insights into A?-interacting proteins are critical for understanding the molecular mechanisms underlying A?-mediated toxicity. We recently undertook an in-depth in vitro interrogation of the A?1-42 interactome using human frontal lobes as the biological source material and taking advantage of advances in mass spectrometry performance characteristics. These analyses uncovered the small cyclic neuropeptide somatostatin (SST) to be the most selectively enriched binder to oligomeric A?1-42. Subsequent validation experiments revealed that SST interferes with A? fibrillization and promotes the formation of A? assemblies characterized by a 50-60 kDa SDS-resistant core. The distributions of SST and A? overlap in the brain and SST has been linked to AD by several additional observations. This perspective summarizes this body of literature and draws attention to the fact that SST is one of several neuropeptide hormones that acquire amyloid properties before their synaptic release. The latter places the interaction between SST and A? among an increasing number of observations that attest to the ability of amyloidogenic proteins to influence each other. A model is presented which attempts to reconcile existing data on the involvement of SST in the AD etiology.

SUBMITTER: Solarski M 

PROVIDER: S-EPMC5871028 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature