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Wikipedia

SORL1

October 20, 2023

Sortilin-related receptor, L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene.[5]

SORL1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSORL1, sortilin-related receptor, L(DLR class) A repeats containing, C11orf32, LR11, LRP9, SORLA, SorLA-1, gp250, sortilin related receptor 1
External IDsOMIM: 602005 MGI: 1202296 HomoloGene: 2336 GeneCards: SORL1
Orthologs
SpeciesHumanMouse
Entrez

6653

20660

Ensembl

ENSG00000137642

ENSMUSG00000049313

UniProt

Q92673

O88307

RefSeq (mRNA)

NM_003105

NM_011436
NM_001357261

RefSeq (protein)

NP_003096

NP_035566
NP_001344190

Location (UCSC)Chr 11: 121.45 – 121.63 MbChr 9: 41.88 – 42.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Schematic diagram of the multiple domains of SORLA, the protein product of the SORL1 gene. The relative orientations of the domains are drawn to match the ectodomain model of Jensen et al., PNAS (2023), which is also shown on the next figure. From Holstege et al., medRxiv (2023).
Schematic and structure model of the ectodomain of SORLA/SORL1, plus its two dimer interfaces in the middle panel, followed by the way the two interfaces can combine to form a polymeric network and how that network can underlie and stabilize the network of retromer arches on the other side of the tubular membrane. From Jensen et al., PNAS (2023). Atomic coordinates of the ectodomain model are available at https://modelarchive.org/doi/10.5452/ma-zgbg4
A model of the endosome tubule showing the characteristic retromer arch polymer wrapping around the outer (cytoplasmic) side and the ectodomain of SORL1 forming a supporting polymeric network inside. The interior SORL1 network is anchored to retromer by a transmembrane helix and a short C-terminal domain that binds to VPS26 (dark green) on the outside.

SORL1 (also known as SORLA, SORLA1, or LR11; SORLA or SORL1 are used, often interchangeably, for the protein product of the SORL1 gene) is a 2214 residue Type I transmembrane protein receptor that binds certain peptides and integral membrane protein cargo in the endolysosomal pathway and delivers them for sorting to the retromer multi protein complex;[6] the gene is predominantly expressed in the central nervous system.[7] Endosomal traffic jams linked to SORL1 retromer dysfunction are the earliest cellular pathology in both familial and the more common sporadic Alzheimer’s patients.[8][9]

Retromer regulates protein trafficking from the early endosome either back to the trans-Golgi (retrograde) or back to the plasma membrane (direct recycling).[10] Two forms of retromer are known: the VPS26A retromer and the VPS26B retromer, the latter being dedicated to direct recycling in the CNS.[11] SORL1 is a multi domain single-pass membrane protein whose large ectodomain resides primarily in endosomal tubules, being connected by its transmembrane helical domain and cytoplasmic tail to the VPS26 retromer subunit on the outer endosomal membrane.[12]

The age at onset of SORL1 mutation carriers varies, which has complicated segregation analyses. Nevertheless, protein−truncating variants (PTVs) are observed almost exclusively in AD patients,[13] indicating that SORL1 is haploinsufficient.[14] However, most variants are rare missense variants that can be benign, or risk−increasing, but recent reports have indicated that some variants are causative for disease.[15][16] In fact, specific missense variants have been observed only in AD cases, some of which may have a dominant negative effect.[17].[1] [2]

ALZFORUM has created an interactive web page that maps all of the currently known variants onto the schematic of the SORLA domain structure shown in the Figure on the right, along with information for each one. It can be accessed at https://www.alzforum.org/mutations/sorl1

Clinical significance Edit

A significant reduction in SORL1 (LR11) expression has been found in brain tissue of Alzheimer's disease patients.[18] Protein levels of retromer subunits have also been found to be reduced in the transentorhinal cortex of sporadic Alzheimer’s patients, the brain region where Alzheimer’s disease begins.[19] SORL1-VPS26B retromer has been linked with regulation of amyloid precursor protein (APP), faulty processing of which is implicated in Alzheimer's.[11][20] SORL1 cargo includes APP and its amyloid forming peptide cleavage products, as well as the important glutamate neurotransmitter receptor subunit GRIA1.[21] SORL1 binds these and other cargo proteins and delivers them to the retromer, an assembly of multiple gene products that is the master regulator of protein trafficking from the early endosome.[22] Studies by a group of international researchers support the proposition that SORL1 plays a part in seniors developing Alzheimer's disease, the findings being significant across racial and ethnic strata.[23] SORL1 is now considered the fourth causal Alzheimer’s gene,[16] the others being APP and the two presenilins PSEN1 and PSEN2 [24] and it is the only one also genetically linked to the common, late-onset sporadic form of the disease.[25] Defective SORL1-retromer protein recycling has been proposed as the “fire” of sporadic Alzheimer’s disease that drives production of amyloid and tau tangle “smoke”, thereby resolving the apparent paradoxical failure of treatments aimed at the latter two to completely arrest the disease.[26]

See also Edit

References Edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000137642 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049313 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Sortilin-related receptor, L(DLR class) A repeats containing".
  6. ^ Small SA, Petsko GA (March 2015). "Retromer in Alzheimer disease, Parkinson disease and other neurological disorders". Nature Reviews. Neuroscience. 16 (3): 126–132. doi:10.1038/nrn3896. PMID 25669742. S2CID 5166260.
  7. ^ Szabo MP, Mishra S, Knupp A, Young JE (January 2022). "The role of Alzheimer's disease risk genes in endolysosomal pathways". Neurobiology of Disease. 162: 105576. doi:10.1016/j.nbd.2021.105576. PMC 9071255. PMID 34871734.
  8. ^ Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA (July 2000). "Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations". The American Journal of Pathology. 157 (1): 277–286. doi:10.1016/S0002-9440(10)64538-5. PMC 1850219. PMID 10880397.
  9. ^ Small SA, Simoes-Spassov S, Mayeux R, Petsko GA (October 2017). "Endosomal Traffic Jams Represent a Pathogenic Hub and Therapeutic Target in Alzheimer's Disease". Trends in Neurosciences. 40 (10): 592–602. doi:10.1016/j.tins.2017.08.003. PMC 5654621. PMID 28962801.
  10. ^ Carosi JM, Denton D, Kumar S, Sargeant TJ (2023). "Receptor Recycling by Retromer". Molecular and Cellular Biology. 43 (7): 317–334. doi:10.1080/10985549.2023.2222053. PMC 10348044. PMID 37350516.
  11. ^ a b Simoes S, Guo J, Buitrago L, Qureshi YH, Feng X, Kothiya M, et al. (December 2021). "Alzheimer's vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling". Cell Reports. 37 (13): 110182. doi:10.1016/j.celrep.2021.110182. PMC 8792909. PMID 34965419.
  12. ^ Lane RF, St George-Hyslop P, Hempstead BL, Small SA, Strittmatter SM, Gandy S (October 2012). "Vps10 family proteins and the retromer complex in aging-related neurodegeneration and diabetes". The Journal of Neuroscience. 32 (41): 14080–14086. doi:10.1523/JNEUROSCI.3359-12.2012. PMC 3576841. PMID 23055476.
  13. ^ Holstege, Henne; van der Lee, Sven J.; Hulsman, Marc; Wong, Tsz Hang; van Rooij, Jeroen GJ; Weiss, Marjan; Louwersheimer, Eva; Wolters, Frank J.; Amin, Najaf; Uitterlinden, André G.; Hofman, Albert; Ikram, M. Arfan; van Swieten, John C.; Meijers-Heijboer, Hanne; van der Flier, Wiesje M. (2017). "Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease: a clinical interpretation strategy". European Journal of Human Genetics. 25 (8): 973–981. doi:10.1038/ejhg.2017.87. ISSN 1476-5438. PMC 5567154.
  14. ^ Verheijen, Jan; Van den Bossche, Tobi; van der Zee, Julie; Engelborghs, Sebastiaan; Sanchez-Valle, Raquel; Lladó, Albert; Graff, Caroline; Thonberg, Håkan; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A.; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Clarimon, Jordi (2016). "A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease". Acta Neuropathologica. 132 (2): 213–224. doi:10.1007/s00401-016-1566-9. ISSN 1432-0533. PMC 4947104. PMID 27026413.
  15. ^ Fazeli E, Child DD, Bucks SA, Stovarsky M, Edwards G, Yu CE, et al. (July 2023). "A familial missense variant in the AD gene SORL1 impairs its maturation and endosomal sorting". bioRxiv: 2023.07.01.547348. doi:10.1101/2023.07.01.547348. PMC 10349966. PMID 37461597.
  16. ^ a b Jensen AM, Raska J, Fojtik P, Monti G, Lunding M, Vochyanova S, et al. (2023). "The SORL1 p. Y1816C variant causes impaired endosomal dimerization and autosomal dominant Alzheimer's disease". medRxiv 10.1101/2023.07.09.23292253v1.
  17. ^ Holstege, Henne; De Waal, Matthijs W. J.; Tesi, Niccolo; Van Der Lee, Sven J.; ADES-consortium; ADSP consortium; StEP-AD consortium; Knight-ADRC; UCSF/NYGC/UAB (2023). "Effect of prioritized SORL1 missense variants supports clinical consideration for familial Alzheimer’s Disease" (Report). Genetic and Genomic Medicine. doi:10.1101/2023.07.13.23292622.
  18. ^ Scherzer CR, Offe K, Gearing M, Rees HD, Fang G, Heilman CJ, et al. (August 2004). "Loss of apolipoprotein E receptor LR11 in Alzheimer disease". Archives of Neurology. 61 (8): 1200–1205. doi:10.1001/archneur.61.8.1200. PMID 15313836.
  19. ^ Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H, et al. (December 2005). "Model-guided microarray implicates the retromer complex in Alzheimer's disease". Annals of Neurology. 58 (6): 909–919. doi:10.1002/ana.20667. PMID 16315276. S2CID 34144181.
  20. ^ Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, et al. (September 2005). "Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein". Proceedings of the National Academy of Sciences of the United States of America. 102 (38): 13461–13466. Bibcode:2005PNAS..10213461A. doi:10.1073/pnas.0503689102. PMC 1224625. PMID 16174740.
  21. ^ Jensen AM, Kitago Y, Fazeli E, Vægter CB, Small SA, Petsko GA, Andersen OM (January 2023). "Dimerization of the Alzheimer's disease pathogenic receptor SORLA regulates its association with retromer". Proceedings of the National Academy of Sciences of the United States of America. 120 (4): e2212180120. Bibcode:2023PNAS..12012180J. doi:10.1073/pnas.2212180120. PMC 9942828. PMID 36652482.
  22. ^ Seaman MN (July 2021). "The Retromer Complex: From Genesis to Revelations". Trends in Biochemical Sciences. 46 (7): 608–620. doi:10.1016/j.tibs.2020.12.009. PMID 33526371. S2CID 231753314.
  23. ^ Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, et al. (February 2007). "The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease". Nature Genetics. 39 (2): 168–177. doi:10.1038/ng1943. PMC 2657343. PMID 17220890.
  24. ^ Andrade-Guerrero J, Santiago-Balmaseda A, Jeronimo-Aguilar P, Vargas-Rodríguez I, Cadena-Suárez AR, Sánchez-Garibay C, et al. (February 2023). "Alzheimer's Disease: An Updated Overview of Its Genetics". International Journal of Molecular Sciences. 24 (4): 3754. doi:10.3390/ijms24043754. PMC 9966419. PMID 36835161.
  25. ^ Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, et al. (September 2021). "A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease". Nature Genetics. 53 (9): 1276–1282. doi:10.1038/s41588-021-00921-z. PMC 10243600. PMID 34493870.
  26. ^ Small SA, Petsko GA (2020). "Endosomal recycling reconciles the Alzheimer's disease paradox". Science Translational Medicine. 12 (572): eabb1717. doi:10.1126/scitranslmed.abb1717. PMC 8025181. PMID 33268506.

External links Edit

October 20, 2023
sorl1, sortilin, related, receptor, class, repeats, containing, protein, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes2dm4, 3g2s, 3g2t, 3wsx, 3wsy, 3wszidentifiersaliases, sortilin, related, receptor, class, repea. Sortilin related receptor L DLR class A repeats containing is a protein that in humans is encoded by the SORL1 gene 5 SORL1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2DM4 3G2S 3G2T 3WSX 3WSY 3WSZIdentifiersAliasesSORL1 sortilin related receptor L DLR class A repeats containing C11orf32 LR11 LRP9 SORLA SorLA 1 gp250 sortilin related receptor 1External IDsOMIM 602005 MGI 1202296 HomoloGene 2336 GeneCards SORL1Gene location Human Chr Chromosome 11 human 1 Band11q24 1Start121 452 314 bp 1 End121 633 763 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 9 A5 1Start41 876 016 bp 2 End42 035 593 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed infrontal polemiddle frontal gyrusinferior ganglion of vagus nerveBrodmann area 23middle temporal gyrusendothelial cellsubthalamic nucleusBrodmann area 10postcentral gyrussuperior vestibular nucleusTop expressed infacial motor nucleuscerebellar vermisconjunctival fornixmedullary collecting ductmedial vestibular nucleuspineal glandanterior horn of spinal cordsubmandibular glandutriclesubstantia nigraMore reference expression dataBioGPSn aGene ontologyMolecular functionamyloid beta binding low density lipoprotein particle binding protein binding transmembrane signaling receptor activityCellular componentintegral component of membrane recycling endosome endosome Golgi apparatus membrane Golgi cisterna integral component of plasma membrane extracellular region trans Golgi network early endosome endoplasmic reticulum low density lipoprotein particle nuclear envelope lumen extracellular exosome Golgi membrane extracellular space endosome membraneBiological processnegative regulation of tau protein kinase activity protein targeting steroid metabolic process positive regulation of choline O acetyltransferase activity lipid transport protein targeting to lysosome negative regulation of neurofibrillary tangle assembly endocytosis positive regulation of protein catabolic process lipid metabolism negative regulation of amyloid beta formation negative regulation of protein oligomerization negative regulation of neurogenesis protein maturation negative regulation of aspartic type endopeptidase activity involved in amyloid precursor protein catabolic process cholesterol metabolic process negative regulation of protein binding positive regulation of ER to Golgi vesicle mediated transport receptor mediated endocytosis positive regulation of early endosome to recycling endosome transport post Golgi vesicle mediated transport negative regulation of MAP kinase activity positive regulation of endocytic recycling regulation of smooth muscle cell migration positive regulation of protein localization to early endosome transport negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process positive regulation of protein exit from endoplasmic reticulum protein retention in Golgi apparatus negative regulation of neuron death signal transductionSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez665320660EnsemblENSG00000137642ENSMUSG00000049313UniProtQ92673O88307RefSeq mRNA NM 003105NM 011436NM 001357261RefSeq protein NP 003096NP 035566NP 001344190Location UCSC Chr 11 121 45 121 63 MbChr 9 41 88 42 04 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseSchematic diagram of the multiple domains of SORLA the protein product of the SORL1 gene The relative orientations of the domains are drawn to match the ectodomain model of Jensen et al PNAS 2023 which is also shown on the next figure From Holstege et al medRxiv 2023 Schematic and structure model of the ectodomain of SORLA SORL1 plus its two dimer interfaces in the middle panel followed by the way the two interfaces can combine to form a polymeric network and how that network can underlie and stabilize the network of retromer arches on the other side of the tubular membrane From Jensen et al PNAS 2023 Atomic coordinates of the ectodomain model are available at https modelarchive org doi 10 5452 ma zgbg4A model of the endosome tubule showing the characteristic retromer arch polymer wrapping around the outer cytoplasmic side and the ectodomain of SORL1 forming a supporting polymeric network inside The interior SORL1 network is anchored to retromer by a transmembrane helix and a short C terminal domain that binds to VPS26 dark green on the outside SORL1 also known as SORLA SORLA1 or LR11 SORLA or SORL1 are used often interchangeably for the protein product of the SORL1 gene is a 2214 residue Type I transmembrane protein receptor that binds certain peptides and integral membrane protein cargo in the endolysosomal pathway and delivers them for sorting to the retromer multi protein complex 6 the gene is predominantly expressed in the central nervous system 7 Endosomal traffic jams linked to SORL1 retromer dysfunction are the earliest cellular pathology in both familial and the more common sporadic Alzheimer s patients 8 9 Retromer regulates protein trafficking from the early endosome either back to the trans Golgi retrograde or back to the plasma membrane direct recycling 10 Two forms of retromer are known the VPS26A retromer and the VPS26B retromer the latter being dedicated to direct recycling in the CNS 11 SORL1 is a multi domain single pass membrane protein whose large ectodomain resides primarily in endosomal tubules being connected by its transmembrane helical domain and cytoplasmic tail to the VPS26 retromer subunit on the outer endosomal membrane 12 The age at onset of SORL1 mutation carriers varies which has complicated segregation analyses Nevertheless protein truncating variants PTVs are observed almost exclusively in AD patients 13 indicating that SORL1 is haploinsufficient 14 However most variants are rare missense variants that can be benign or risk increasing but recent reports have indicated that some variants are causative for disease 15 16 In fact specific missense variants have been observed only in AD cases some of which may have a dominant negative effect 17 1 2 ALZFORUM has created an interactive web page that maps all of the currently known variants onto the schematic of the SORLA domain structure shown in the Figure on the right along with information for each one It can be accessed at https www alzforum org mutations sorl1 Contents 1 Clinical significance 2 See also 3 References 4 External linksClinical significance EditA significant reduction in SORL1 LR11 expression has been found in brain tissue of Alzheimer s disease patients 18 Protein levels of retromer subunits have also been found to be reduced in the transentorhinal cortex of sporadic Alzheimer s patients the brain region where Alzheimer s disease begins 19 SORL1 VPS26B retromer has been linked with regulation of amyloid precursor protein APP faulty processing of which is implicated in Alzheimer s 11 20 SORL1 cargo includes APP and its amyloid forming peptide cleavage products as well as the important glutamate neurotransmitter receptor subunit GRIA1 21 SORL1 binds these and other cargo proteins and delivers them to the retromer an assembly of multiple gene products that is the master regulator of protein trafficking from the early endosome 22 Studies by a group of international researchers support the proposition that SORL1 plays a part in seniors developing Alzheimer s disease the findings being significant across racial and ethnic strata 23 SORL1 is now considered the fourth causal Alzheimer s gene 16 the others being APP and the two presenilins PSEN1 and PSEN2 24 and it is the only one also genetically linked to the common late onset sporadic form of the disease 25 Defective SORL1 retromer protein recycling has been proposed as the fire of sporadic Alzheimer s disease that drives production of amyloid and tau tangle smoke thereby resolving the apparent paradoxical failure of treatments aimed at the latter two to completely arrest the disease 26 See also EditAPP Presenilin GRIA1 Retromer VPS26B VPS26A Endosome Protein targeting Lysosome Alzheimer s diseaseReferences Edit a b c GRCh38 Ensembl release 89 ENSG00000137642 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000049313 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene Sortilin related receptor L DLR class A repeats containing Small SA Petsko GA March 2015 Retromer in Alzheimer disease Parkinson disease and other neurological disorders Nature Reviews Neuroscience 16 3 126 132 doi 10 1038 nrn3896 PMID 25669742 S2CID 5166260 Szabo MP Mishra S Knupp A Young JE January 2022 The role of Alzheimer s disease risk genes in endolysosomal pathways Neurobiology of Disease 162 105576 doi 10 1016 j nbd 2021 105576 PMC 9071255 PMID 34871734 Cataldo AM Peterhoff CM Troncoso JC Gomez Isla T Hyman BT Nixon RA July 2000 Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer s disease and Down syndrome differential effects of APOE genotype and presenilin mutations The American Journal of Pathology 157 1 277 286 doi 10 1016 S0002 9440 10 64538 5 PMC 1850219 PMID 10880397 Small SA Simoes Spassov S Mayeux R Petsko GA October 2017 Endosomal Traffic Jams Represent a Pathogenic Hub and Therapeutic Target in Alzheimer s Disease Trends in Neurosciences 40 10 592 602 doi 10 1016 j tins 2017 08 003 PMC 5654621 PMID 28962801 Carosi JM Denton D Kumar S Sargeant TJ 2023 Receptor Recycling by Retromer Molecular and Cellular Biology 43 7 317 334 doi 10 1080 10985549 2023 2222053 PMC 10348044 PMID 37350516 a b Simoes S Guo J Buitrago L Qureshi YH Feng X Kothiya M et al December 2021 Alzheimer s vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling Cell Reports 37 13 110182 doi 10 1016 j celrep 2021 110182 PMC 8792909 PMID 34965419 Lane RF St George Hyslop P Hempstead BL Small SA Strittmatter SM Gandy S October 2012 Vps10 family proteins and the retromer complex in aging related neurodegeneration and diabetes The Journal of Neuroscience 32 41 14080 14086 doi 10 1523 JNEUROSCI 3359 12 2012 PMC 3576841 PMID 23055476 Holstege Henne van der Lee Sven J Hulsman Marc Wong Tsz Hang van Rooij Jeroen GJ Weiss Marjan Louwersheimer Eva Wolters Frank J Amin Najaf Uitterlinden Andre G Hofman Albert Ikram M Arfan van Swieten John C Meijers Heijboer Hanne van der Flier Wiesje M 2017 Characterization of pathogenic SORL1 genetic variants for association with Alzheimer s disease a clinical interpretation strategy European Journal of Human Genetics 25 8 973 981 doi 10 1038 ejhg 2017 87 ISSN 1476 5438 PMC 5567154 Verheijen Jan Van den Bossche Tobi van der Zee Julie Engelborghs Sebastiaan Sanchez Valle Raquel Llado Albert Graff Caroline Thonberg Hakan Pastor Pau Ortega Cubero Sara Pastor Maria A Benussi Luisa Ghidoni Roberta Binetti Giuliano Clarimon Jordi 2016 A comprehensive study of the genetic impact of rare variants in SORL1 in European early onset Alzheimer s disease Acta Neuropathologica 132 2 213 224 doi 10 1007 s00401 016 1566 9 ISSN 1432 0533 PMC 4947104 PMID 27026413 Fazeli E Child DD Bucks SA Stovarsky M Edwards G Yu CE et al July 2023 A familial missense variant in the AD gene SORL1 impairs its maturation and endosomal sorting bioRxiv 2023 07 01 547348 doi 10 1101 2023 07 01 547348 PMC 10349966 PMID 37461597 a b Jensen AM Raska J Fojtik P Monti G Lunding M Vochyanova S et al 2023 The SORL1 p Y1816C variant causes impaired endosomal dimerization and autosomal dominant Alzheimer s disease medRxiv 10 1101 2023 07 09 23292253v1 Holstege Henne De Waal Matthijs W J Tesi Niccolo Van Der Lee Sven J ADES consortium ADSP consortium StEP AD consortium Knight ADRC UCSF NYGC UAB 2023 Effect of prioritized SORL1 missense variants supports clinical consideration for familial Alzheimer s Disease Report Genetic and Genomic Medicine doi 10 1101 2023 07 13 23292622 Scherzer CR Offe K Gearing M Rees HD Fang G Heilman CJ et al August 2004 Loss of apolipoprotein E receptor LR11 in Alzheimer disease Archives of Neurology 61 8 1200 1205 doi 10 1001 archneur 61 8 1200 PMID 15313836 Small SA Kent K Pierce A Leung C Kang MS Okada H et al December 2005 Model guided microarray implicates the retromer complex in Alzheimer s disease Annals of Neurology 58 6 909 919 doi 10 1002 ana 20667 PMID 16315276 S2CID 34144181 Andersen OM Reiche J Schmidt V Gotthardt M Spoelgen R Behlke J et al September 2005 Neuronal sorting protein related receptor sorLA LR11 regulates processing of the amyloid precursor protein Proceedings of the National Academy of Sciences of the United States of America 102 38 13461 13466 Bibcode 2005PNAS 10213461A doi 10 1073 pnas 0503689102 PMC 1224625 PMID 16174740 Jensen AM Kitago Y Fazeli E Vaegter CB Small SA Petsko GA Andersen OM January 2023 Dimerization of the Alzheimer s disease pathogenic receptor SORLA regulates its association with retromer Proceedings of the National Academy of Sciences of the United States of America 120 4 e2212180120 Bibcode 2023PNAS 12012180J doi 10 1073 pnas 2212180120 PMC 9942828 PMID 36652482 Seaman MN July 2021 The Retromer Complex From Genesis to Revelations Trends in Biochemical Sciences 46 7 608 620 doi 10 1016 j tibs 2020 12 009 PMID 33526371 S2CID 231753314 Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F et al February 2007 The neuronal sortilin related receptor SORL1 is genetically associated with Alzheimer disease Nature Genetics 39 2 168 177 doi 10 1038 ng1943 PMC 2657343 PMID 17220890 Andrade Guerrero J Santiago Balmaseda A Jeronimo Aguilar P Vargas Rodriguez I Cadena Suarez AR Sanchez Garibay C et al February 2023 Alzheimer s Disease An Updated Overview of Its Genetics International Journal of Molecular Sciences 24 4 3754 doi 10 3390 ijms24043754 PMC 9966419 PMID 36835161 Wightman DP Jansen IE Savage JE Shadrin AA Bahrami S Holland D et al September 2021 A genome wide association study with 1 126 563 individuals identifies new risk loci for Alzheimer s disease Nature Genetics 53 9 1276 1282 doi 10 1038 s41588 021 00921 z PMC 10243600 PMID 34493870 Small SA Petsko GA 2020 Endosomal recycling reconciles the Alzheimer s disease paradox Science Translational Medicine 12 572 eabb1717 doi 10 1126 scitranslmed abb1717 PMC 8025181 PMID 33268506 External links EditSORL1 references from NCBI Study Detects a Gene Linked to Alzheimer s N Wade New York Times Jan 15 2007 https www alzforum org news research news sorting out sorl1 500 mutations mapped prioritized alzforum dataset https www alzforum org news research news when missense variants derail sorl1 traffic destination dementia https modelarchive org doi 10 5452 ma zgbg4 https www alzforum org mutations sorl1 Retrieved from https en wikipedia org w index php title SORL1 amp oldid 1179684137, wikipedia, wiki, book, books, library,

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