count	source_label	source_id	relationship	target_label	target_id	entity_type	solr_id	publication_id	sentences
7	LAMB1_DROME	UNIPROT:P11046	activates		UNIPROT:P05067	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	Since LanB1 did not affect BiP levels in the context of neuronal Aβ, and since LanB1 could rescue Aβ toxicity independently of Xbp1, LanB1 must have acted independently of the IRE1α/XBP1s arm of the ER stress response pathway.|||Since glia are the other major cell type in the adult fly brains and can produce laminins, we determined if LanB1 overexpression in these cells could also rescue Aβ toxicity.|||To assess if BiP reduction was behind the LanB1 rescue of Aβ toxicity, we examined BiP mRNA and protein levels.|||We confirmed that LanB1 co-expression (either usingUAS-LanB1EP-600orUAS-LanB1:RFP) significantly rescued Aβ toxicity.|||As LanB1 co-expression induced the most consistent and pronounced rescue of AβArctoxicity, we took this line forward for further study.|||LanB1 upregulation, via either UAS-LanB1EP-600or UAS-LanB1:RFP, caused an equivalently pronounced rescue of Aβ toxicity.|||LanB1 also rescued Aβ toxicity in combination with other laminin subunits and a collagen IV subunit and acted independently of the IRE1α/XBP1s ER stress response branch.
2	LAMB1_DROME	UNIPROT:P11046	decreases		UNIPROT:P05067	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	Intriguingly, LanB1 was able to substantially rescue Aβ toxicity without altering levels of Aβ, either soluble or insoluble, and also without reducing the secretion of Aβ into the extracellular milieu, indicating that LanB1 expression increased neuronal resistance to Aβ toxicity.|||LanB1 does not reduce secretion of Aβ from neurons Since Aβ protein levels, both soluble and insoluble, were not reduced in LanB1 co-expressing flies, we hypothesized that the intracellular accumulation of LanB1 might have prevented the normal secretion of the toxic Aβ peptide into the extracellular space, despite the presence of a signal peptide.
2	LAMB1_DROME	UNIPROT:P11046	activates		UNIPROT:P17861	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	However, LanB1 could rescue the enhanced toxicity of Aβ+Xbp1RNAiin adult neurons, indicating that LanB1 could act independently of Xbp1.|||Since LanB1 did not affect BiP levels in the context of neuronal Aβ, and since LanB1 could rescue Aβ toxicity independently of Xbp1, LanB1 must have acted independently of the IRE1α/XBP1s arm of the ER stress response pathway.
1	LAMB1_DROME	UNIPROT:P11046	activates		UNIPROT:P03372	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	Discussion Here, we showed that ectopic, neuronal overexpression of laminin (and collagen IV) monomers provided robust protection in anin vivo Drosophilamodel of AD, and that ectopic overexpression of LanB1 resulted in ER retention in these neurons.
1	LAMB1_DROME	UNIPROT:P11046	increases		UNIPROT:P05067	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	LanB1 could therefore rescue multiple toxic effects of Aβ expression.
1	LAMB1_DROME	UNIPROT:P11046	inhibits		UNIPROT:P11021	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	Intriguingly, BiP may be a molecular chaperone of laminin assembly in the ER (Kumagai and Kitagawa, 1997), which may indicate that LanB1 overexpression sequesters BiP from having toxic effects when upregulated chronically.
1	LAMB1_DROME	UNIPROT:P11046	increases		UNIPROT:P11021	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	It is possible that BiP expression was at the upper limit and LanB1 could not increase BiP expression further.
1	LAMB1_DROME	UNIPROT:P11046	increases		UNIPROT:P11046	Protein	53b1b5a2-ab64-11e6-90f5-001a4ae51247	26818504	We hypothesized that if accumulation of LanB1 results in ER accumulation, then overexpression of LanB1 in perineurial glia using a UAS-LanB1 [an EP insertion in LanB1,LanB1[EP-600], that drives LanB1 expression (de Celis and Molnar, 2010)] would result in ER aggregates.
1	LAMB1_DROME	UNIPROT:P11046	inhibits		GO:0016477	Phenotype	7a6bacb4-ae94-11ec-840e-0050569a791b	PMCPMC8167899	Loss of LanB1 has been noted to produce delays in midgut cell migration (Urbano et al., 2009), while defects in both midgut migration and repolarization have been noted in LanB2 mutants (Wolfstetter and Holz, 2012), supporting a role for laminins in mediating some or all aspects of midgut migration and MET.Midgut cells migrate in a stereotypical and coordinated manner as a heterogenous population of epithelial-like and mesenchymal cells (Campbell and Casanova, 2015).
1	LAMB1_DROME	UNIPROT:P11046	activates		MESH:D059865	Phenotype	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	LanB1 rescue of Aβ toxicity is independent of the BiP/Xbp1 ER stress response pathway Aβ induces ER stress markers, including the ER chaperone BiP, and leads to increased alternative splicing of Xbp1 (Casas-Tinto et al., 2011; Marcora et al., 2017; Niccoli et al., 2016).
1	LAMB1_DROME	UNIPROT:P11046	activates		MESH:D059865	Phenotype	53b1b5a2-ab64-11e6-90f5-001a4ae51247	26818504	The partial rescue in glial swelling due to LanB1 heterodeficiency supports the hypothesis that unbound LanB1 is acting as a misfolded protein in the ER to induce the unfolded protein response and ER stress.
1	LAMB1_DROME	UNIPROT:P11046	activates		GO:0007631	Phenotype	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	AβArcflies ingested a significantly smaller amount of food over 7 days compared to uninduced controls, while LanB1 co-expression completely rescued feeding behavior to uninduced levels (Fig. 2E).
1	LAMB1_DROME	UNIPROT:P11046	decreases		MESH:D010455	Phenotype	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	LanB1 does not reduce secretion of Aβ from neurons Since Aβ protein levels, both soluble and insoluble, were not reduced in LanB1 co-expressing flies, we hypothesized that the intracellular accumulation of LanB1 might have prevented the normal secretion of the toxic Aβ peptide into the extracellular space, despite the presence of a signal peptide.
1		UNIPROT:Q5JRA6	increases	LAMB1_DROME	UNIPROT:P11046	Protein	f70a9972-cc46-11e7-8943-001a4a160176	PMC5715762	We found that the defective secretion of both LanA and LanB1 caused by lack of Tango1 was rescued by also silencingdpy(SI Appendix, Figs.
1		UNIPROT:P15215	increases	LAMB1_DROME	UNIPROT:P11046	Protein	0d08e8de-c6da-11ee-b22c-0050569a1f61	10.1016/j.neurobiolaging.2023.09.008	As with LanB1 overexpression, expression of LanB2:GFP rescued Aβ toxicity (Fig. 8Aand quantified inFig.
1		UNIPROT:P11046	increases	LAMB1_DROME	UNIPROT:P11046	Protein	53b1b5a2-ab64-11e6-90f5-001a4ae51247	26818504	We hypothesized that if accumulation of LanB1 results in ER accumulation, then overexpression of LanB1 in perineurial glia using a UAS-LanB1 [an EP insertion in LanB1,LanB1[EP-600], that drives LanB1 expression (de Celis and Molnar, 2010)] would result in ER aggregates.