Therapeutic Delivery of Butyrylcholinesterase by Brain-Wide Viral Gene Transfer to Mice
Open accessAbstract
Recent research shows that butyrylcholinesterase (BChE) is not simply a liver enzyme that detoxifies bioactive esters in food and medications. In fact, in pursuing other goals, we recently found that it has an equally important role in regulating the peptide hormone ghrelin and its impact on hunger, obesity, and emotions. Here, we present and examine means of manipulating brain BChE levels by viral gene transfer, either regionally or globally, to modulate ghrelin signaling for long-term therapeutic purposes and to set the stage for exploring the neurophysiological impact of such an intervention.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An intracerebral injection avoids the tissue barrier that the blood-CSF barrier or blood-brain-barrier represents and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain.
“An intracerebral injection avoids the tissue barrier that blood-cerebrospinal fluid (CSF) barrier or blood-brain-barrier (BBB) represents, and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain (4, 20, 22, 26, 27).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [26]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A new and rapid colorimetric determination of acetylcholinesterase activity
Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961) · Biochemical Pharmacology · doi:10.1016/0006-2952(61)90145-9 · Cited by 27,221 · see citing works
Guide for the Care and Use of Laboratory Animals
Rowan, A. N. (1996) · Journal of Medical Primatology · doi:10.1159/000460187 · Cited by 20,451 · see citing works
Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
Deverman, B. E., Pravdo, P. L., Simpson, B. P., Kumar, S. R., Chan, K. Y., Banerjee, A., Wu, W.-L., Yang, B., Huber, N., Pasca, S. P., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3440 · Cited by 1,061 · see citing works
Antibody-based protection against HIV infection by vectored immunoprophylaxis
Balazs, A. B., Chen, J., Hong, C. M., Rao, D. S., Yang, L., & Baltimore, D. (2012) · Nature · doi:10.1038/nature10660 · Cited by 545 · cited 1× · see citing works
“cDNA encoding luciferase (Luc) or mouse BChE was subcloned into pAAV-VIP plasmid [8,11].”
MethodLockridge, O. (2015) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2014.11.011 · Cited by 399 · see citing works
Li, B., Stribley, J. A., Ticu, A., Xie, W., Schopfer, L. M., HAMMOND, P. I., Brimijoin, S., Hinrichs, S. H., & Lockridge, O. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.751320.x · Cited by 354 · cited 1× · see citing works
“To address these issues, we are conducting a range of BChE gene transfer experiments in wild-type C57BL mice and BChE knockouts (KO) engineered to eliminate expression [9].”
MethodSelf-citationRe-engineering Butyrylcholinesterase as a Cocaine Hydrolase
Sun, H., Pang, Y., Lockridge, O., & Brimijoin, S. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.2.220 · Cited by 149 · see citing works
Self-citationBrimijoin, S., Gao, Y., Anker, J. J., Gliddon, L. A., LaFleur, D. W., Shah, R. R., Zhao, Q., Singh, M., & Carroll, M. E. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301666 · Cited by 137 · see citing works
Self-citationPlasma butyrylcholinesterase regulates ghrelin to control aggression
Chen, V. P., Gao, Y., Geng, L., Parks, R. J., Pang, Y., & Brimijoin, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421536112 · Cited by 110 · cited 2× · see citing works
“That proved correct in a sense, but the side-effects that emerged in our study appeared to be positive rather than negative, in the sense that they led to a reduction of in-cage fighting and significantly longer life spans in male mice, which were ultimately traced to ghrelin reduction [8].”
BackgroundMethodSelf-citationParaoxonase-1 and Early-Life Environmental Exposures
Marsillach, J., Costa, L. G., & Furlong, C. E. (2016) · Annals of Global Health · doi:10.1016/j.aogh.2016.01.009 · Cited by 68 · cited 1× · see citing works
“It seems to have evolved in order to inactivate natural toxins in food sources, and in the modern age it appears able to protect us from chemical warfare agents and pesticides [1,2].”
BackgroundLong-acting cocaine hydrolase for addiction therapy
Chen, X.-B., Xue, L., Hou, S., et al. (2015) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1517713113 · Cited by 61
Geng, L., Gao, Y., Chen, X.-B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067446 · Cited by 41
Self-citationXue, L., Hou, S., Tong, M., et al. (2013) · Biochemical Journal · doi:10.1042/bj20130549 · Cited by 40
Flagged first, then by citations
1 of the 14 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306 · see citing works
Huang, Q., Chan, K. Y., Tobey, I. G., Chan, Y. A., Poterba, T., Boutros, C. L., Balazs, A. B., Daneman, R., Bloom, J. M., Seed, C., et al. (2019) · PLOS ONE · doi:10.1371/journal.pone.0225206 · Cited by 234 · see citing works
“eB have been applied across a wide range of neuroscience experiments in mice [5,9,10], including genetic deficit correction [11,12] and neurological disease modeling [13].”
BackgroundCholinesterases and the fine line between poison and remedy
Pope, C., & Brimijoin, S. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.01.044 · Cited by 138 · see citing works
“In addition, using a novel “PHP gene transfer vector” that readily crosses the blood-brain barrier [138], we found it possible to generate very high and essentially permanent BChE expression across virtually all regions of the cerebral cortex, cerebellum, and basal ganglia [139].”
Self-citationChowdhury, E. A., Meno‐Tetang, G. M. L., Chang, H. Y., Wu, S., Huang, H. W., Jamier, T., Chandran, J. S., & Shah, D. K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.01.017 · Cited by 78 · see citing works
Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection
Tuma, J., Chen, Y.-J., Collins, M. G., Paul, A., Li, J., Han, H., Sharma, R., Murthy, N., & Lee, H. Y. (2023) · Biochemistry · doi:10.1021/acs.biochem.3c00371 · Cited by 65 · see citing works
Arotçarena, M.-L., Doveró, S., Biendon, N., Dutheil, N., Planche, V., Bézard, E., & Dehay, B. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.762209 · Cited by 21 · see citing works
“, 2016) and transduces most brain cells (approximately 50–100% of neurons and 80% of astrocytes) across multiple CNS regions after peripheral delivery in mice (Deverman et al., 2016; Allen et al., 2017; Gao et al., 2017; Morabito et al., 2017; Hordeaux et al., 2018; Rincon et al., 2018) and rats (Jackson et al.”
BackgroundImproved systemic AAV gene therapy with a neurotrophic capsid in Niemann–Pick disease type C1 mice
Davidson, C. D., Gibson, A. L., Gu, T., Baxter, L. L., Deverman, B. E., Beadle, K., Incao, A. A., Rodriguez‐Gil, J. L., Fujiwara, H., Jiang, X., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202101040 · Cited by 23 · see citing works
“B vectors have demonstratedwidespread and efficient gene delivery to the rodent CNS and alleviation of neurological phenotypes (Jackson et al, 2016; Gao et al, 2017; Morabito et al, 2017; Zelikowsky et al, 2018; Lim et al, 2019; Luoni et al, 2020; Yang et al, 2020).”
BackgroundPidaný, F., Křoustková, J., al Mamun, A., et al. (2023) · European journal of medicinal chemistry · doi:10.2139/ssrn.4360512 · Cited by 13
Čadež, T., & Kovarik, Z. (2020) · Periodicum biologorum · doi:10.18054/pb.v121-122i1-2.10867 · Cited by 7
- Authors
- Gao, Y., Geng, L., Chen, V., & Brimijoin, S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Brimijoin, Stephen
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2017-07-08
- Volume
- 22
- Issue
- 7
- Pages
- 1145
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC5963683
- OpenAlex
- W2728917033
- Semantic Scholar
- b7ff9269c02f48e8e13608c82a54bc3164eef065
- Cited by
- 12
- References
- 14
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institutes of Health
- National Institute on Drug Abuse (UG3DA042492, DP1DA031340)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- butyrylcholinesterase, viral gene delivery, ghrelin signaling, neuropharmacology
- MeSH terms
- Animals, Brain, Butyrylcholinesterase, Emotions, Genetic Vectors, Humans, Obesity, Genetic Therapy, Gene Transfer Techniques, Mice, Ghrelin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
