Sorting receptor SORLA: cellular mechanisms and implications for disease

Schmidt, Vanessa; Subkhangulova, Aygul; Willnow, Thomas E.

doi:10.1007/s00018-016-2410-z

Cited by 50 publications

(42 citation statements)

References 81 publications

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“…As a sorting protein receptor, Sorl1 can trap APP in the Golgi. Sorl1 can also shuttle APP in the early endosome and the Golgi, upregulating pathways that form soluble APP, downregulating those that form insoluble amyloid, and inhibiting Aβ production and its accumulation in the brain [ 29 ]. Thus, Sorl1 is considered the key factor in the pathogenesis of Alzheimer’s disease (AD).…”

Section: Discussionmentioning

confidence: 99%

“…For example, as a ceRNA, lncRNA NONMMUT055714 competes for binding to miR-7684-5p, thereby affecting Sorl1 expression. Sorl1 increases Aβ production in the brains of elderly patients, increasing AD risk [ 29 ]. Additionally, Aβ over-deposition can trigger oxidative stress and autophagy, induce neuronal apoptosis and pro-inflammatory cytokine-dependent activation of glial cells, cause synaptic dysfunction, and accelerate abnormal phosphorylation of tau proteins, thus promoting POCD [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

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Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction

et al. 2017

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Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. Using microarray analyses, we comprehensively compared long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) expression profiles in hippocampal tissues from a mouse model of POCD and control mice. A total of 175 lncRNAs, 117 mRNAs, and 26 miRNAs were differentially expressed between POCD and control mice. Gene ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of dysregulated genes. Correlated coding-noncoding co-expression (CNC) and competing endogenous RNA (ceRNA) expression networks were constructed using bioinformatics methods. lncRNA NONMMUT000708 correlated positively with expression of the inflammation-related gene Hif3a. lncRNAs NONMMUT043249 and NONMMUT028705 mediated gene expression by binding the transcription factor cAMP response element-binding protein (CREB). The constructed ceRNA network suggested lncRNA NONMMUT055714 binds competitively with miR-7684-5p, increasing expression of its target gene, Sorl1. Finally, eight dysregulated lncRNAs, four miRNAs, and ten mRNAs were confirmed via quantitative real-time polymerase chain reaction (PCR) in 10 POCD-healthy mouse paired samples. These results suggest that lncRNAs and miRNAs are involved in POCD pathogenesis and progression. Our ceRNA network will improve understanding of lncRNA-mediated ceRNA regulatory mechanisms operating during the pathogenesis of POCD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction

et al. 2017

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“…Subsequently, internalized SORL1 receptors generally shuttle between the TGN and endosomes, guided by cytosolic adaptor proteins which will be discussed later in this review in the context of A␤PP trafficking (Fig. 2) (reviewed in [41,42]).…”

Section: Sorl1 Encodes a Membrane-bound Receptor With Multiple Functimentioning

confidence: 99%

Sorting Out the Role of the Sortilin-Related Receptor 1 in Alzheimer’s Disease

Barthelson

Newman

Lardelli

2020

Journal of Alzheimer's Disease Reports

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Sortilin-related receptor 1 (SORL1) encodes a large, multi-domain containing, membrane-bound receptor involved in endosomal sorting of proteins between the trans-Golgi network, endosomes and the plasma membrane. It is genetically associated with Alzheimer's disease (AD), the most common form of dementia. SORL1 is a unique gene in AD, as it appears to show strong associations with the common, late-onset, sporadic form of AD and the rare, early-onset familial form of AD. Here, we review the genetics of SORL1 in AD and discuss potential roles it could play in AD pathogenesis.

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“…The ICD of SorLA is important for retrograde trafficking from endosomes to the trans-Golgi network (TGN) by binding to the retromer complex and anterograde trafficking by interacting with clathrin-adaptors (Jacobsen et al, 2002 ; Seaman, 2007 ; Fjorback et al, 2012 ). SorLA binds APP and Aβ to control their transport from endosomes either to the TGN to prevent proteolytic APP-breakdown or to lysosomes for Aβ-degradation, which recently has been reviewed in detail by Schmidt et al ( 2016 ). The mosaic receptor has different extracellular binding domains: an N-terminal Vps10p domain followed by an EGF-precursor homology domain and 11 LBRs.…”

Section: Sorla (Sorl1/lr11/lrp11)mentioning

confidence: 99%

“…The SorLA propeptide is removed in late Golgi compartments by furin (Munck Petersen et al, 1999 ). SorLA and its interaction with APP have recently been reviewed in detail by Schmidt et al ( 2016 ).…”

Section: Sorla (Sorl1/lr11/lrp11)mentioning

confidence: 99%

Functional Roles of the Interaction of APP and Lipoprotein Receptors

Pohlkamp

Wasser

Herz

2017

Front. Mol. Neurosci.

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The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD.

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Sorting receptor SORLA: cellular mechanisms and implications for disease

Cited by 50 publications

References 81 publications

Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction

Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction

Sorting Out the Role of the Sortilin-Related Receptor 1 in Alzheimer’s Disease

Functional Roles of the Interaction of APP and Lipoprotein Receptors

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