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Gamma-secretase plays an important role in the development of Alzheimer disease (AD). Gamma-secretase activity is enriched in autophagic vacuoles and it augments amyloid-beta (Abeta) synthesis. Autophagy-lysosomal dysfunction has been implicated in AD, but whether gamma-secretase activity is affected by autophagy remains unclear. Here we report that(More)
Caspase plays an important role in apoptosis and physiological processes such as synaptic plasticity. However, the caspase substrate at the synapse is still unknown. Here we used an in vitro cleavage assay with a small-pool human brain cDNA library. We identified the presynaptic protein Caytaxin as a substrate of caspase-3 and caspase-7. Deficiency in(More)
The endoplasmic reticulum (ER) copes with unfolded proteins in the lumen (ER stress) by activating three distinct intracellular signaling pathways of unfolded protein response (UPR). ER stress contributes to the pathogenesis of obesity and diabetes, which are risk factors for Alzheimer's disease (AD) that accelerate the pathogenesis of AD. However, whether(More)
Prune homolog 2 (Drosophila) (PRUNE2) encodes a BCH motif-containing protein that shares homology with the Cayman ataxia-related protein Caytaxin. Caytaxin is a substrate of caspase-3 and is specifically expressed at the presynapse of vesicular-type glutamate transporter (VGLUT)-positive neurons, where it plays a role in glutamate neurotransmission(More)
A family of Bcl-2/adenovirus E1B 19kDa-interacting proteins (BNIPs) plays critical roles in several cellular processes such as cellular transformation, apoptosis, neuronal differentiation, and synaptic function, which are mediated by the BNIP2 and Cdc42GAP homology (BCH) domain. Prune homolog 2 (Drosophila) (PRUNE2) and its isoforms -C9orf65, BCH(More)
The endoplasmic reticulum (ER) plays a pivotal role in cellular functions such as the ER stress response. However, the effect of the ER membrane on caspase activation remains unclear. This study reveals that polyglutamine oligomers augmented at ER induce insertion of Bax into the ER membrane, thereby activating caspase-7. In line with the role of ER in cell(More)
Cos 7 cells transfected with human atrial natriuretic polypeptide (hANP) gene with SV40 enhancer and replication origin sequences expressed hANP gene. The expressed RNA was indistinguishable from native hANP mRNA and the transcribed protein seemed to be properly processed to alpha-hANP and beta-hANP. This system provides a useful approach to investigate the(More)
To investigate whether the human atrial natriuretic polypeptide (hANP) gene is responsive to glucocorticoid, we co-introduced the hANP gene (with SV40 enhancer) with HSV-tk gene into mouse tk- L cells. The transformants with hANP gene with SV40 enhancer expressed hANP specific RNAs. The administration of 1 microM dexamethasone reduced the expressed hANP(More)
Leucine-rich repeat kinase (LRRK2) is the causal molecule of autosomal dominant Parkinson's disease (PD). We previously reported that intracellular degradation of wild-type (WT) LRRK2 is promoted by formation of heterodimers with the I2020T mutant LRRK2. In the present study, we investigated whether this is also the case for mouse/human cross-species(More)
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