Proteomics as a tool for discovery: proteins implicated in Alzheimer's disease are highly expressed in normal pancreatic islets.
A proteomic analysis of islets was undertaken to determine the protein constituents of normal adult mouse islets. Unexpectedly, we identified several islet proteins that are associated with the pathogenesis of Alzheimer's disease. Some of these proteins had chaperone activity that is integral to proper protein folding. This group includes GRP78, valosin-containing protein, calreticulin, protein disulfide isomerase, DnaK, HSP70, HSP60, and TCP-1. Additionally, neuronal proteins key to coordinated neuronal guidance and survival were also identified in islets. This group includes proprotein convertase subtilisin, collapsin response mediator protein 2, ubiquinol-cytochrome c reductase core protein, L-3-hydroxyacyl-Coenzyme A dehydrogenase, glutamine synthetase, peroxiredoxin, and secretogogin. An important subset of the proteins identified here has not been reported previously in pancreatic islets. Abnormal activity of these proteins in brain may contribute to the pathogenesis of Alzheimer's disease, a neurodegenerative condition characterized by focal amyloid deposits with neurofibrillary tangles. The putative role of these proteins in Alzheimer's pathogenesis is intriguing given the possible clinical relationship and pathological similarity of Alzheimer's disease to type 2 diabetes. These findings have therefore led to the hypothesis that these proteins may also play a role in type 2 diabetes.
Nicolls
Mark R
MR
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Barbara Davis Center for Childhood Diabetes, Denver, Colorado 80262, USA. mark.nicolls@uchsc.edu
D'Antonio
Jason M
JM
Hutton
John C
JC
Gill
Ronald G
RG
Czwornog
Jennifer L
JL
Duncan
Mark W
MW
D000544:Alzheimer Disease / Q000209:etiology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D007515:Islets of Langerhans / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D011506:Proteins