Psychiatry related information on Ncstn

• Presenilin-1 and nicastrin, two components of gamma-secretase associated with Alzheimer's disease plaques, are present in the synapses of the brain and in various peripheral organs, including skeletal muscle [1].

High impact information on Ncstn

• Presenilin forms an active gamma-secretase complex together with Nicastrin (NCT), APH-1, and PEN-2, which among other substrates cleaves the beta-amyloid precursor protein (beta-APP) generating the amyloid beta-peptide and the beta-APP intracellular domain [2].
• Here we have identified dual targeting sequences (for endoplasmic reticulum and mitochondria) in NCT and showed expression of NCT in mitochondria by immunoelectron microscopy [2].
• In addition, active sites of synaptogenesis, the base of the external granular layer and glomeruli, contained PS1 fragments and smaller amount of NCT [3].
• Furthermore, protease protection assays confirmed that nicastrin is contained in the outer lysosomal membrane, rather than in an internalized vesicle awaiting degradation, and that it is properly orientated with its amino-terminus facing the lysosomal lumen with its carboxyl-terminus facing the cytosol [4].
• The immunoreactivities of both presenilin-1 and nicastrin were also observed at the sarcolemma of muscle fibers [1].

Anatomical context of Ncstn

• Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria [2].
• Previous reports have localized presenilin and nicastrin to the endoplasmic reticulum [4].
• In contrast, no significant difference in the nicastrin protein level was observed between normal and denervated muscle fibers [1].
• In the present study, we examined the expression pattern of presenilin-1 and nicastrin in normal and denervated hindlimb muscles of the rat [1].

Analytical, diagnostic and therapeutic context of Ncstn

• Immunoblotting for NCT revealed the expected mature and immature species, which gradually declined during development [3].
• Immunoprecipitation of NCT indicated its physical association with PS1 fragments [3].
• However, during a proteomics-based characterization of lysosomal membrane proteins, a major spot observed on silver-stained IEF/SDS-PAGE gels was identified by mass spectrometric sequencing as nicastrin [4].
• Normal distribution of presenilin-1 and nicastrin in skeletal muscle and the differential responses of these proteins after denervation [1].

References