Tomoregulin (TMEFF2) Binds XXXX Amyloid-b (Ab) Oligomer and @entity15370 and Protects Neurons from Ab-Induced @entity137 .

@entity15370 @entity137 @entity44831 @entity573 @entity19 @entity2359 @entity195 @entity528 @entity71276
Amyloid-b (Ab) protein causes @entity2359 and its abnormal aggregation into amyloid is a pathological hallmark of @entity195 ( @entity195 ). Cellular proteins able to interact with Ab or its precursor, @entity15370 ( @entity15370 ), may regulate Ab production and @entity2359 . We identified a brain-enriched @entity71276 , tomoregulin (TR), that directly binds Ab and Ab oligomers ( @entity44831 ). TR co-immunoprecipitated with Ab and @entity44831 in cultured cells and co-localized with amyloid plaques and intraneuronal Ab in the 5xFAD @entity195 @entity19 model. TR was also enriched in astrocytic processes reactive to amyloid plaques. Surface plasmon resonance spectroscopy studies showed that the extracellular domain of TR binds to @entity44831 with a high affinity ( @entity573 =76.8 nM). Electron paramagnetic resonance spectroscopy also demonstrated a physical interaction between spin-labeled Ab and the TR extracellular domain in solution. Furthermore, TR also interacted with @entity15370 and enhanced its cleavage by a-secretase. Both cellular expression of TR and application of recombinant TR extracellular domain protected N2a neurons from @entity44831 -induced @entity528 . These data provide first evidence that neuronal and astrocytic expression of TR is intimately related to Ab metabolism and @entity137 , and could be neuroprotective through its direct interaction with Ab and  @entity15370 .
