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Article ; Online: Retromer Proteins Reduced in Down Syndrome and the Dp16 Model: Impact of APP Dose and Preclinical Studies of a γ-Secretase Modulator.

Chen, Xu-Qiao / Sawa, Mariko / Becker, Ann / Karachentsev, Dmitry / Zuo, Xinxin / Rynearson, Kevin D / Tanzi, Rudolph E / Mobley, William C

Annals of neurology

2023 Volume 94, Issue 2, Page(s) 245–258

Abstract: Objective: The retromer complex plays an essential role in intracellular endosomal sorting. Deficits in the retromer complex are linked to enhanced Aβ production. The levels of the components of the retromer complex are reported to be downregulated in ... ...

Abstract	Objective: The retromer complex plays an essential role in intracellular endosomal sorting. Deficits in the retromer complex are linked to enhanced Aβ production. The levels of the components of the retromer complex are reported to be downregulated in Alzheimer disease (AD). Down syndrome (DS) shares neuropathological features with AD. Recent evidence points to dysregulation of the retromer complex in DS. The mechanisms underlying retromer deficits in DS and AD are poorly understood. Methods: We measured the levels of retromer components in the frontal cortex of cases of DS-AD (AD in DS) as well as DS; the frontal cortex of a person partially trisomic (PT-DS) for human chromosome 21 (HSA21), whose genome had only the normal 2 copies of the APP gene, was also examined. We also analyzed these proteins in the Dp16 mouse model of DS. To further explore the molecular mechanism for changes in the retromer complex, we treated Dp16 mice with a γ-secretase modulator (GSM; 776890), a treatment that reduces the levels of Aβ42 and Aβ40. Results: We found VPS26A, VPS26B, and VPS29, but not VPS35, were significantly reduced in both DS and DS-AD, but not in PT-DS. Downregulation of VPS26A, VPS26B, and VPS29 was recapitulated in the brains of old Dp16 mice (at 16 months of age) and required increased App gene dose. Significantly, GSM treatment completely prevented reductions of the retromer complex. Interpretation: Our studies point to increased APP gene dose as a compromising retromer function in DS and suggest a causal role for Aβ42 and Aβ40. ANN NEUROL 2023;94:245-258.
MeSH term(s)	Animals ; Humans ; Mice ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid Precursor Protein Secretases ; Down Syndrome/drug therapy ; Down Syndrome/metabolism ; Endosomes/metabolism ; Protein Transport ; Vesicular Transport Proteins/genetics
Chemical Substances	Amyloid Precursor Protein Secretases (EC 3.4.-) ; Vesicular Transport Proteins ; APP protein, human ; APP protein, mouse
Language	English
Publishing date	2023-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26659
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Article ; Online: Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease.

Caldwell, Andrew B / Liu, Qing / Zhang, Can / Schroth, Gary P / Galasko, Douglas R / Rynearson, Kevin D / Tanzi, Rudolph E / Yuan, Shauna H / Wagner, Steven L / Subramaniam, Shankar

Alzheimer's & dementia : the journal of the Alzheimer's Association

2022 Volume 18, Issue 11, Page(s) 2117–2130

Abstract: While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic ... ...

Abstract	While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic dysregulation. Screening strategies based on mechanistic, multi-omics approaches that go beyond pathological readouts can aid in the evaluation of therapeutics. Using early-onset Alzheimer's (EOFAD) disease patient lineage PSEN1
MeSH term(s)	Humans ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Amyloid beta-Peptides/metabolism ; Plaque, Amyloid/pathology ; Induced Pluripotent Stem Cells/metabolism
Chemical Substances	Amyloid Precursor Protein Secretases (EC 3.4.-) ; Amyloid beta-Protein Precursor ; Amyloid beta-Peptides
Language	English
Publishing date	2022-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12553
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Article ; Online: The GSM BPN-15606 as a Potential Candidate for Preventative Therapy in Alzheimer's Disease.

Prikhodko, Olga / Rynearson, Kevin D / Sekhon, Travis / Mante, Mike M / Nguyen, Phuong D / Rissman, Robert A / Tanzi, Rudolph E / Wagner, Steven L

Journal of Alzheimer's disease : JAD

2020 Volume 73, Issue 4, Page(s) 1541–1554

Abstract: Background: In the amyloid hypothesis of Alzheimer's disease (AD), the dysregulation of amyloid-β protein (Aβ) production and clearance leads to amyloid deposits, tau tangles, neuronal loss, and cognitive dysfunction. Thus far, therapies targeting the ... ...

Abstract	Background: In the amyloid hypothesis of Alzheimer's disease (AD), the dysregulation of amyloid-β protein (Aβ) production and clearance leads to amyloid deposits, tau tangles, neuronal loss, and cognitive dysfunction. Thus far, therapies targeting the enzymes responsible for Aβ production have been found ineffective or having significant side effects. Objective: To test whether a γ-secretase modulator, BPN-15606, is an effective disease-modifying or preventative treatment in the PSAPP mouse model of AD. Methods: We treated pre-plaque (3-month-old) and post-plaque (6-month-old) PSAPP AD transgenic mice for 3 months and examined behavioral, biochemical, and pathological end points. Results: BPN-15606 attenuated cognitive impairment and reduced amyloid plaque load, microgliosis, and astrogliosis associated with the AD phenotype of PSAPP mice when administered to pre-plaque (3-month-old) but was ineffective when administered to post-plaque (6-month-old) mice. No treatment-related toxicity was observed. Conclusion: BPN-15606 appears efficacious when administered prior to significant pathology.
MeSH term(s)	Alzheimer Disease/prevention & control ; Alzheimer Disease/psychology ; Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Amyloid beta-Protein Precursor/genetics ; Animals ; Behavior, Animal/drug effects ; Cognitive Dysfunction/prevention & control ; Cognitive Dysfunction/psychology ; Gliosis ; Humans ; Maze Learning/drug effects ; Memory/drug effects ; Mice ; Mice, Transgenic ; Motor Activity/drug effects ; Phenethylamines/adverse effects ; Phenethylamines/therapeutic use ; Plaque, Amyloid/genetics ; Plaque, Amyloid/prevention & control ; Postural Balance/drug effects ; Psychomotor Performance/drug effects ; Pyridazines/adverse effects ; Pyridazines/therapeutic use
Chemical Substances	APP protein, human ; Amyloid beta-Protein Precursor ; BPN-15606 ; Phenethylamines ; Pyridazines ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2020-01-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-190442
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Article ; Online: γ-Secretase Partitioning into Lipid Bilayers Remodels Membrane Microdomains after Direct Insertion.

Barros, Marilia / Houlihan, William J / Paresi, Chelsea J / Brendel, Matthew / Rynearson, Kevin D / Lee, Chang-Wook / Prikhodko, Olga / Cregger, Cristina / Chang, Geoffrey / Wagner, Steven L / Gilchrist, M Lane / Li, Yue-Ming

Langmuir : the ACS journal of surfaces and colloids

2020 Volume 36, Issue 23, Page(s) 6569–6579

Abstract: γ-Secretase is a multisubunit complex that catalyzes intramembranous cleavage of transmembrane proteins. The lipid environment forms membrane microdomains that serve as spatio-temporal platforms for proteins to function properly. Despite substantial ... ...

Abstract	γ-Secretase is a multisubunit complex that catalyzes intramembranous cleavage of transmembrane proteins. The lipid environment forms membrane microdomains that serve as spatio-temporal platforms for proteins to function properly. Despite substantial advances in the regulation of γ-secretase, the effect of the local membrane lipid microenvironment on the regulation of γ-secretase is poorly understood. Here, we characterized and quantified the partitioning of γ-secretase and its substrates, the amyloid precursor protein (APP) and Notch, into lipid bilayers using solid-supported model membranes. Notch substrate is preferentially localized in the liquid-disordered (L
MeSH term(s)	Amyloid Precursor Protein Secretases ; Amyloid beta-Protein Precursor ; Lipid Bilayers ; Membrane Lipids ; Membrane Microdomains
Chemical Substances	Amyloid beta-Protein Precursor ; Lipid Bilayers ; Membrane Lipids ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2020-06-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.0c01178
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Article ; Online: Nanopore-based conformational analysis of a viral RNA drug target.

Shasha, Carolyn / Henley, Robert Y / Stoloff, Daniel H / Rynearson, Kevin D / Hermann, Thomas / Wanunu, Meni

ACS nano

2014 Volume 8, Issue 6, Page(s) 6425–6430

Abstract: Nanopores are single-molecule sensors that show exceptional promise as a biomolecular analysis tool by enabling label-free detection of small amounts of sample. In this paper, we demonstrate that nanopores are capable of detecting the conformation of an ... ...

Abstract	Nanopores are single-molecule sensors that show exceptional promise as a biomolecular analysis tool by enabling label-free detection of small amounts of sample. In this paper, we demonstrate that nanopores are capable of detecting the conformation of an antiviral RNA drug target. The hepatitis C virus uses an internal ribosome entry site (IRES) motif in order to initiate translation by docking to ribosomes in its host cell. The IRES is therefore a viable and important drug target. Drug-induced changes to the conformation of the HCV IRES motif, from a bent to a straight conformation, have been shown to inhibit HCV replication. However, there is presently no straightforward method to analyze the effect of candidate small-molecule drugs on the RNA conformation. In this paper, we show that RNA translocation dynamics through a 3 nm diameter nanopore is conformation-sensitive by demonstrating a difference in transport times between bent and straight conformations of a short viral RNA motif. Detection is possible because bent RNA is stalled in the 3 nm pore, resulting in longer molecular dwell times than straight RNA. Control experiments show that binding of a weaker drug does not produce a conformational change, as consistent with independent fluorescence measurements. Nanopore measurements of RNA conformation can thus be useful for probing the structure of various RNA motifs, as well as structural changes to the RNA upon small-molecule binding.
MeSH term(s)	Binding Sites ; Electrodes ; Electrolytes ; Fluorescence Resonance Energy Transfer ; Hepacivirus ; Hydrogen-Ion Concentration ; Molecular Conformation ; Nanoparticles/chemistry ; Nanopores ; Nanotechnology/methods ; Nucleic Acid Hybridization ; RNA/chemistry ; RNA, Viral/chemistry ; Ribosomes/chemistry ; Temperature
Chemical Substances	Electrolytes ; RNA, Viral ; RNA (63231-63-0)
Language	English
Publishing date	2014-05-29
Publishing country	United States
Document type	Journal Article
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/nn501969r
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Article: Screening for inhibitors of the hepatitis C virus internal ribosome entry site RNA

Zhou, Shou / Rynearson, Kevin D / Ding, Kejia / Brunn, Nicholas D / Hermann, Thomas

Bioorganic & medicinal chemistry. 2013 Oct. 15, v. 21, no. 20

2013

Abstract: The highly conserved internal ribosome entry site (IRES) of hepatitis C virus (HCV) regulates translation of the viral RNA genome and is essential for the expression of HCV proteins in infected host cells. The structured subdomain IIa of the IRES element ...

Abstract	The highly conserved internal ribosome entry site (IRES) of hepatitis C virus (HCV) regulates translation of the viral RNA genome and is essential for the expression of HCV proteins in infected host cells. The structured subdomain IIa of the IRES element is the target site of recently discovered benzimidazole inhibitors that selectively block viral translation through capture of an extended conformation of an RNA internal loop. Here, we describe the development of a FRET-based screening assay for similarly acting HCV translation inhibitors. The assay relies on monitoring fluorescence changes that indicate rearrangement of the RNA target conformation upon ligand binding. Screening of a small pilot set of potential RNA binders identified a benzoxazole scaffold as a ligand that bound selectively to IIa IRES target and was confirmed as an inhibitor of in vitro viral translation. The screening approach outlined here provides an efficient method to discover HCV translation inhibitors that may provide leads for the development of novel antiviral therapies directed at the highly conserved IRES RNA.
Keywords	Hepatitis C virus ; RNA ; benzimidazole ; chemistry ; fluorescence ; genome ; monitoring ; proteins ; ribosomes ; screening ; translation (genetics)
Language	English
Dates of publication	2013-1015
Size	p. 6139-6144.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2013.03.054
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators.

Rynearson, Kevin D / Buckle, Ronald N / Herr, R Jason / Mayhew, Nicholas J / Chen, Xinchao / Paquette, William D / Sakwa, Samuel A / Yang, Jinhai / Barnes, Keith D / Nguyen, Phuong / Mobley, William C / Johnson, Graham / Lin, Juinn H / Tanzi, Rudolph E / Wagner, Steven L

Bioorganic & medicinal chemistry

2020 Volume 28, Issue 22, Page(s) 115734

Abstract: The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a ... ...

Abstract	The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a methoxypyridine motif within the tetracyclic scaffold provided compounds with improved activity for arresting Aβ42 production as well as improved properties, including solubility. In vivo pharmacokinetic analysis demonstrated that several compounds within the novel series were capable of crossing the BBB and accessing the therapeutic target. Treatment with methoxypyridine-derived compound 64 reduced Aβ42 levels in the plasma of J20 mice, in addition to reducing Aβ42 levels in the plasma and brain of Tg2576 mice.
MeSH term(s)	Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Peptides/analysis ; Amyloid beta-Peptides/antagonists & inhibitors ; Amyloid beta-Peptides/biosynthesis ; Animals ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Design ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Male ; Mice ; Mice, Transgenic ; Molecular Structure ; Pyridines/chemical synthesis ; Pyridines/chemistry ; Pyridines/pharmacology ; Structure-Activity Relationship
Chemical Substances	Amyloid beta-Peptides ; Enzyme Inhibitors ; Pyridines ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2020-09-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2020.115734
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Article ; Online: Molecular imaging of Alzheimer's disease-related gamma-secretase in mice and nonhuman primates.

Xu, Yulong / Wang, Changning / Wey, Hsiao-Ying / Liang, Yingxia / Chen, Zude / Choi, Se Hoon / Ran, Chongzhao / Rynearson, Kevin D / Bernales, Daniela R / Koegel, Robert E / Fiedler, Stephanie A / Striar, Robin / Wagner, Steven L / Tanzi, Rudolph E / Zhang, Can

The Journal of experimental medicine

2020 Volume 217, Issue 12

Abstract: The pathogenesis of Alzheimer's disease (AD) is primarily driven by brain accumulation of the amyloid-β-42 (Aβ42) peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. γ-Secretase is a prime drug target for AD; ...

Abstract	The pathogenesis of Alzheimer's disease (AD) is primarily driven by brain accumulation of the amyloid-β-42 (Aβ42) peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. γ-Secretase is a prime drug target for AD; however, its brain regional expression and distribution remain largely unknown. Here, we are aimed at developing molecular imaging tools for visualizing γ-secretase. We used our recently developed γ-secretase modulators (GSMs) and synthesized our GSM-based imaging agent, [11C]SGSM-15606. We subsequently performed molecular imaging in rodents, including AD transgenic animals, and macaques, which revealed that our probe displayed good brain uptake and selectivity, stable metabolism, and appropriate kinetics and distribution for imaging γ-secretase in the brain. Interestingly, rodents and macaques shared certain brain areas with high γ-secretase expression, suggesting a functional conservation of γ-secretase. Collectively, we have provided the first molecular brain imaging of γ-secretase, which may not only accelerate our drug discovery for AD but also advance our understanding of AD.
MeSH term(s)	Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/enzymology ; Amyloid Precursor Protein Secretases/metabolism ; Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Brain/pathology ; Humans ; Macaca mulatta ; Magnetic Resonance Imaging ; Male ; Mice, Transgenic ; Molecular Imaging ; Positron Emission Tomography Computed Tomography ; Presenilin-1/metabolism
Chemical Substances	Presenilin-1 ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2020-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20182266
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Article ; Online: Screening for inhibitors of the hepatitis C virus internal ribosome entry site RNA.

Zhou, Shou / Rynearson, Kevin D / Ding, Kejia / Brunn, Nicholas D / Hermann, Thomas

Bioorganic & medicinal chemistry

2013 Volume 21, Issue 20, Page(s) 6139–6144

Abstract	The highly conserved internal ribosome entry site (IRES) of hepatitis C virus (HCV) regulates translation of the viral RNA genome and is essential for the expression of HCV proteins in infected host cells. The structured subdomain IIa of the IRES element is the target site of recently discovered benzimidazole inhibitors that selectively block viral translation through capture of an extended conformation of an RNA internal loop. Here, we describe the development of a FRET-based screening assay for similarly acting HCV translation inhibitors. The assay relies on monitoring fluorescence changes that indicate rearrangement of the RNA target conformation upon ligand binding. Screening of a small pilot set of potential RNA binders identified a benzoxazole scaffold as a ligand that bound selectively to IIa IRES target and was confirmed as an inhibitor of in vitro viral translation. The screening approach outlined here provides an efficient method to discover HCV translation inhibitors that may provide leads for the development of novel antiviral therapies directed at the highly conserved IRES RNA.
MeSH term(s)	Antiviral Agents/pharmacology ; Base Sequence ; Benzimidazoles/pharmacology ; Benzoxazoles/pharmacology ; Fluorescence Resonance Energy Transfer ; Genome, Viral ; Hepacivirus/chemistry ; Hepacivirus/genetics ; Mass Screening ; Models, Molecular ; Molecular Sequence Data ; RNA, Viral/antagonists & inhibitors ; RNA, Viral/chemistry ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Ribosomes/drug effects ; Ribosomes/genetics ; Ribosomes/metabolism ; Signal Transduction
Chemical Substances	Antiviral Agents ; Benzimidazoles ; Benzoxazoles ; RNA, Viral
Language	English
Publishing date	2013-04-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2013.03.054
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Article ; Online: Preclinical validation of a potent γ-secretase modulator for Alzheimer's disease prevention.

The Journal of experimental medicine

2021 Volume 218, Issue 4

Abstract: A potent γ-secretase modulator (GSM) has been developed to circumvent problems associated with γ-secretase inhibitors (GSIs) and to potentially enable use in primary prevention of early-onset familial Alzheimer's disease (EOFAD). Unlike GSIs, GSMs do not ...

Abstract	A potent γ-secretase modulator (GSM) has been developed to circumvent problems associated with γ-secretase inhibitors (GSIs) and to potentially enable use in primary prevention of early-onset familial Alzheimer's disease (EOFAD). Unlike GSIs, GSMs do not inhibit γ-secretase activity but rather allosterically modulate γ-secretase, reducing the net production of Aβ42 and to a lesser extent Aβ40, while concomitantly augmenting production of Aβ38 and Aβ37. This GSM demonstrated robust time- and dose-dependent efficacy in acute, subchronic, and chronic studies across multiple species, including primary and secondary prevention studies in a transgenic mouse model. The GSM displayed a >40-fold safety margin in rats based on a comparison of the systemic exposure (AUC) at the no observed adverse effect level (NOAEL) to the 50% effective AUC or AUCeffective, the systemic exposure required for reducing levels of Aβ42 in rat brain by 50%.
MeSH term(s)	Alzheimer Disease/enzymology ; Alzheimer Disease/prevention & control ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Cell Line, Tumor ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical/methods ; Female ; Humans ; Macaca fascicularis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Peptide Fragments/metabolism ; Phenethylamines/administration & dosage ; Pyridazines/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Treatment Outcome
Chemical Substances	Amyloid beta-Peptides ; BPN-15606 ; Peptide Fragments ; Phenethylamines ; Pyridazines ; amyloid beta-protein (1-42) ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2021-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20202560
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