Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease
Open accessAbstract
Histone deacetylase inhibitors (HDACIs) alter gene expression epigenetically by interfering with the normal functions of HDAC. Given their ability to decrease Aβ levels, HDACIs area potential treatment for Alzheimer's disease (AD). However, it is unclear how HDACIs alter Aβ levels. We developed two novel HDAC inhibitors with improved pharmacological properties, such as a longer half-life and greater penetration of the blood-brain barrier: mercaptoacetamide-based class II HDACI (coded as W2) and hydroxamide-based class I and IIHDACI (coded as I2) and investigated how they affect Aβ levels and cognition. HDACI W2 decreased Aβ40 and Aβ42 in vitro. HDACI I2 also decreased Aβ40, but not Aβ42. We systematically examined the molecular mechanisms by which HDACIs W2 and I2 can decrease Aβ levels. HDACI W2 decreased gene expression of γ-secretase components and increased the Aβ degradation enzyme Mmp2. Similarly, HDACI I2 decreased expression of β- and γ-secretase components and increased mRNA levels of Aβ degradation enzymes. HDACI W2 also significantly decreased Aβ levels and rescued learning and memory deficits in aged hAPP 3x Tg AD mice. Furthermore, we found that the novel HDACI W2 decreased tau phosphorylation at Thr181, an effect previously unknown for HDACIs. Collectively, these data suggest that class II HDACls may serve as a novel therapeutic strategy for AD.
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Written from the paper’s full text.
TL;DR
Novel mercaptoacetamide-based class II HDAC inhibitor W2 lowers Aβ levels, reduces tau phosphorylation at Thr181, and improves learning and memory in hAPP 3xTg AD mice. The study also identifies transcriptional downregulation of Aβ-producing enzymes and upregulation of Aβ-degrading enzymes as possible mechanisms.
Key findings
- In N2a-APP cells, W2 decreased human Aβ40 and Aβ42 by 20%, while I2 significantly decreased Aβ40 but not Aβ42; W2 or I2 also decreased rodent Aβ40 by 20% in primary cortical neurons.
- W2 increased cell surface APP by 33% at 2 hrs and both W2 and I2 increased it about twofold at 24 hrs; in vivo, W2 increased sAPPα and decreased sAPPβ.
- In 9–10 month old hAPP 3xTg AD mice, W2 (50 mg/kg daily i.p.) decreased soluble Aβ40 after 2 weeks and decreased soluble and insoluble Aβ40 and Aβ42 after 4 weeks; W2 also reduced Thr181 phospho-tau by approximately 50% without changing total tau or tau kinases.
- W2 improved learning and memory in wild-type mice and rescued cognitive deficits in 9–10 month old hAPP 3xTg AD mice, as shown by increased platform crossings without altered swim speed.
Methods
- In vitro: N2a cells overexpressing hAPP, primary rat cortical and hippocampal neurons, Aβ ELISA, cell surface biotinylation, live cell surface staining, and qPCR for Aβ synthesis/degradation genes.
- In vivo: 9–10 month old hAPP 3xTg AD mice and 2–3 month old wild-type mice received W2 (50 mg/kg, daily i.p.) or control for 2 or 4 weeks; brain Aβ was measured by DEA/FA fractionation and ELISA, with immunoblotting for APP cleavage products and tau phosphorylation.
- Behavior: Morris water maze assessed spatial learning and memory; statistics used two-tailed t-tests or one-way ANOVA with Tukey’s post-hoc, and two-way ANOVA for escape latencies, with significance at p<0.05.
Limitations
- The paper states that the lowest optimal dose of HDACIs and additional molecular mechanisms affecting cognitive performance are still being investigated.
- Evident from the text: I2 was not tested in vivo; W2 was selected for in vivo work because it was more effective in reducing Aβ in vitro, so the in vivo findings apply only to W2.
- Evident from the text: the study reports cognitive rescue in the 3xTg AD model but does not establish whether the effects generalize to other AD models or to human AD.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
4 of 6 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured
- Premisecitation
APP located at the cell surface is more likely to undergo α-secretase cleavage to produce sAPPα, thereby reducing Aβ production.
“Thus, APP located at the cell surface is more likely to undergo α-secretase cleavage to produce sAPPα, thereby reducing Aβ production.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites De Strooper, et al., 2010 source
The α-Secretases, Biological activity section says α-secretase cleavage produces soluble APPsα and can reduce Aβ production, although the latter finding has not been universally replicated. It does not say that APP at the cell surface is more likely to undergo this cleavage than APP elsewhere. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Findingown data
In primary cortical neurons, W2 (5 μM) for 24 hrs increased cell surface levels of APP.
“We observed a similar increase in surface levels of APP with HDACI W2 (n=3, Figs. 2E, F).”
Quote in the paperSubstantial claim - Findingown data
In vitro, HDACI W2 had a greater effect on reducing Aβ levels compared to I2.
“Since we observed a greater effect on Aβ levels by treating with HDACI W2 compared to I2in vitro, we continued to examine the effect of HDACI W2 on Aβ production in vivo.”
Quote in the paperSubstantial claim - Findingown data
In 9-10 month old hAPP 3xTg AD mice injected with W2 (50 mg/kg daily i.p.) for 4 weeks, W2 improved learning and memory as evidenced by increased number of platform crossings without altering swim speed.
“We found that W2 treatment improved learning and memory in 9-10 month old hAPP 3x Tg AD mice as evidenced by increased number of platform crossings without altering swim speed (Figs. 6E-H, n=12/group).”
Quote in the paperSubstantial claim - Findingown data
In primary cortical neurons treated with 5 μM I2 for 24 hrs, I2 significantly repressed expression of β-secretase component BACE1 and γ-secretase components Nicastrin and Psen2.
“while I2 significantly repressed expression of β-(BACE1) and γ-secretase components (Nicastrin and Psen2) (Figs.3C, D).”
Quote in the paperSubstantial claim
- Findingown data
In primary cortical neurons, HDACI I2 increased expression of Nep, Ece1, Mmp2, Ctsd and Ctsb.
“while HDACI I2 increased Nep, Ece1, Mmp2, Ctsd and Ctsb expression (Figs. 3E, F).”
Quote in the paperSubstantial claim - Findingown data
In primary cortical neurons treated with 5 μM W2 for 24 hrs, W2 significantly decreased mRNA levels of γ-secretase components Psen1, Psen2, and Nicastrin.
“Further experiments demonstrated that W2 significantly decreased mRNA levels of γ-secretase components (Psen1, Psen2, and Nicastrin)”
Quote in the paperSubstantial claim - Findingown data
In N2a-APP cells, W2 (5 μM) significantly increased cell surface APP within 2 hrs by 33%.
“Quantification of immunoblot results demonstrated that W2 (5 μM) significantly increased cell surface APP within 2 hrs (n=3; by 33 %, *P<0.05, Figs. 2A, B).”
Quote in the paperSubstantial claim - Findingown data
In primary cortical neurons, HDACI W2 or I2 significantly decreased rodent Aβ40 levels by 20%.
“we examined rodent Aβ levels in primary cortical neurons following HDACI treatment, and found that HDACI W2 or I2 significantly decreased rodent Aβ40 (by 20%, Figs. 1E, F; n=6-8).”
Quote in the paperSubstantial claim - Findingown data
In hAPP 3xTg AD mice injected with W2 for 4 weeks, W2 did not alter tau phosphorylation at Thr231, other serine residues, or total tau level.
“However, W2 did not alter tau phosphorylation at the Thr231 site, other serine residues, or the total level of tau (Figs. 5D-F).”
Quote in the paperNot a substantial claim - Findingown data
In N2a-APP cells, I2 (5 μM) did not alter cell surface APP compared to control at 2 hrs of treatment.
“However, I2 (5 μM) did not alter cell surface APP compared to control at 2 hrs of treatment (Figs. 2A, B).”
Quote in the paperNot a substantial claim - Findingown data
In N2a-APP cells, after 24 hrs of treatment, both W2 and I2 (5 μM) significantly increased cell surface APP by two fold.
“After 24 hrs of treatment, both W2 and I2 (5 μM) significantly increased cell surface APP by two fold (n=3; **P<0.01) (Figs. 2C, D).”
Quote in the paperSubstantial claim - Findingown data
In hAPP 3xTg AD mice injected with W2 for 4 weeks, W2 did not change levels of tau kinases P-CDK5, CDK5, P-GSK3β (Y216), and GSK3β.
“We found that W2 did not change levels of these tau kinases (Figs. 5A-C, n=4).”
Quote in the paperNot a substantial claim - Findingown data
In primary hippocampal neurons transfected with GFP and APP, 1 μM or 5 μM W2 for 24 hrs significantly increased cell surface APP by two fold compared to control.
“1 μM or 5μM W2 significantly increased cell surface APP by two fold (n=10; ***P<0.001), compared to control (Figs. 2G, H).”
Quote in the paperSubstantial claim - Findingown data
In 9-10 month old hAPP 3xTg AD mice injected with W2 daily i.p. for 4 weeks, W2 dramatically decreased soluble and insoluble Aβ40 and Aβ42 levels compared to control.
“HDACI W2 treatment dramatically decreased soluble and insoluble Aβ40 and Aβ42 levels, compared to control-injected mice after daily 4 week treatments (Figs. 4C, D, n=10/group, data shown as percentage of soluble Aβ levels in control injected mice).”
Quote in the paperSubstantial claim - Findingown data
In N2a-APP cells, HDACI W2 treatment (1 or 5 μM for 24 h) decreased human Aβ40 and Aβ42 levels by 20%.
“HDACI W2 treatment resulted in a 20% decrease in human Aβ40 and Aβ42 levels (Figs. 1A,B; n=6).”
Quote in the paperSubstantial claim - Interpretationown data
Class II HDACI W2 selectively decreases tau phosphorylation.
“In addition, Class II HDACI W2 selectively decreases tau phosphorylation.”
Quote in the paperSubstantial claim - Interpretationown data
The two novel HDACIs, Class II W2 and Class I and II I2, may have better therapeutic potential compared to other HDACIs, due to their ability to modulate both the production and the degradation of Aβ.
“The two novel HDACIs, Class IIW2 and Class I and II I2, may have better therapeutic potential compared to other HDACIs, due to their ability to modulate both the production and the degradation of Aβ.”
Quote in the paperSubstantial claim- Rests on an assumption: Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
- Interpretationown data
Class II HDACIs may serve as a novel therapeutic strategy for AD.
“Collectively, these data suggest that class II HDACls may serve as a novel therapeutic strategy for AD.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings in mouse models of AD translate to therapeutic benefit in human dementias, including AD.
- Interpretationown data
The novel HDACI W2 affects Aβ production by modulating APP trafficking.
“Taken together, these data suggest that our novel HDACI affects Aβ production by modulating APP trafficking.”
Quote in the paperSubstantial claim - Interpretationown data
The novel HDACI W2 can rescue the memory deficits exhibited in aged hAPP 3xTg AD mice.
“This data suggests that our novel HDACI W2 can rescue the memory deficits exhibited in aged hAPP 3x Tg AD mice.”
Quote in the paperSubstantial claim- Rests on an assumption: 9-10 month old hAPP 3xTg AD mice exhibit mild cognitive impairment.
- Interpretationreasoning
The novel compound Class II HDACI W2 may have the potential to alleviate critical neuropathogenic processes in dementias, including AD, providing broad-spectrum therapeutic benefits.
“Taken together, these data demonstrate that our novel compound Class II HDACI W2 mayhave the potential toalleviatecritical neuropathogenic processes in dementias, including AD, providing broad-spectrum therapeutic benefits.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings in mouse models of AD translate to therapeutic benefit in human dementias, including AD.
- May combine two claims. 10
- Classified as probably not a substantial claim. 1
- The quote only partly states this claim. 1
May combine two claims.
Premisenone givenThe novel HDAC inhibitors W2 (mercaptoacetamide-based class II) and I2 (hydroxamide-based class I and II) have improved pharmacological properties, including longer half-life and greater blood-brain barrier penetration, compared to commercially available HDACIs.
“We developed two novel HDAC inhibitors with improved pharmacological properties, such as a longer half-life and greater penetration of the blood-brain barrier: mercaptoacetamide-based class II HDACI (coded as W2) and hydroxamide-based class I and IIHDACI (coded as I2)”
Quote in the paperSubstantial claim2 of 3 sources checked- cites Konsoula and Jung, 2008 source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites Konsoula, et al., 2009 source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites Konsoula, et al., 2011 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeveral recent studies reported that commercially available HDACIs alter Aβ levels by an unknown mechanism.
“Interestingly, several recent studies reported that the commercially available HDACIs alter Aβ levels by an unknown mechanism (Kilgore et al., 2010;Ricobaraza et al., 2011).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites Kilgore et al., 2010 source
The Results and Discussion report that HDAC inhibitors restored memory performance in APP/PS1 mice, while the Discussion mentions elevated Aβ in the context of Alzheimer’s pathology. Neither those passages nor searches for treatment-related changes in amyloid levels show that the inhibitors altered Aβ levels or discuss a mechanism for such a change. (LLM, conf=0.73)
Experimental — accuracy not yet measured - cites Ricobaraza et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Findingown dataIn 9-10 month old hAPP 3xTg AD mice injected with 50 mg/kg W2 daily i.p. for 2 weeks, W2 significantly decreased soluble Aβ40 levels compared to control, but did not change soluble Aβ42 levels.
“HDACI W2 treatment significantly decreased soluble Aβ40 levels compared to control-injected mice, but there was no change in soluble Aβ42 levels (Figs.4A, B, n=10/group).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataIn primary cortical neurons, HDACI W2 treatment significantly increased Mmp2 expression.
“Additionally, we observed that HDACI W2 treatment significantly increased Mmp2 expression”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn 2-3 month old wild-type mice injected with W2 (50 mg/kg daily i.p.) for 4 weeks, W2 improved learning and memory as evidenced by increased time spent in target quadrant and number of platform crossings without altering swim speed.
“We initially injected 2-3 month old wild-type mice for 4 weeks with W2 (50 mg/kg, daily i.p.) or control (10% DMSO), and found that W2 treated wild-type mice had improved learning and memory as evidenced by increased time spent in the target quadrant and number of platform crossings without altering swim speed (Figs. 6A-D, n=12/group).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn hAPP 3xTg AD mice injected with W2 for 4 weeks, W2 specifically reduced phosphorylation of tau at Thr181, with approximately 50% decrease in Thr181 phospho-tau protein.
“Interestingly, HDACI W2 specifically reduced phosphorylation of tau at the Thr181 site (Figs. 5D-F, n=4).”
- Also stated in: § Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice · plain
“Quantification of these blots revealed that the HDACI W2 induced an approximately 50% decrease in levels of the Thr181 phospho-tau protein (Fig. 5F, n=4/group).”
Quote in the paperSubstantial claim- Also stated in: § Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice · plain
May combine two claims.
Findingown dataIn N2a-APP cells, 5 μM I2 significantly decreased human Aβ40 levels but did not change human Aβ42 levels compared to control.
“Interestingly, 5 μM I2 significantly decreased human Aβ40 levels in N2a-APP cells; however, there were no changes in human Aβ42 levels compared to control (Figs. 1C,D; n=6).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn hAPP 3xTg AD mice injected with 50 mg/kg W2 daily i.p. for 4 weeks, W2 significantly increased sAPPα and significantly decreased sAPPβ compared to control.
“HDACI W2 treatment significantly increased sAPPα and significantly decreased sAPPβ, compared to the control group (Figs.4E, F, n=3/group).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataHDAC inhibition decreased expression of genes involved in Aβ production and induced expression of Aβ degradation enzymes.
“HDAC inhibition decreased expression of genes involved in Aβ production and induced expression of Aβ degradation enzymes.”
Quote in the paperSubstantial claim- Rests on an assumption: HDAC inhibitors alter gene expression epigenetically by interfering with normal HDAC functions.
- Rests on an assumption: Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
- Rests on an assumption: W2 and I2 inhibit HDACs in the tested systems.
May combine two claims.
Interpretationown dataThe novel HDACIs W2 and I2 have dual effects of down-regulating Aβ production pathways while simultaneously up-regulating Aβ clearance mechanisms.
“Taken together, our data suggest that our novel compounds have dual effects of down-regulating Aβ production pathways while simultaneously up-regulating Aβ clearance mechanisms.”
Quote in the paperSubstantial claim- Rests on an assumption: Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
May combine two claims.
Interpretationown dataThe novel HDACI W2 both decreases Aβ levels and modulates tau phosphorylation at Thr181 in vivo.
“Collectively, these data suggest that our novel HDACI W2 not only affected Aβ levels, but also modulated tau phosphorylation at Thr181in vivo.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe novel Class II HDACI W2 decreases Aβ levels and improves learning and memory.
“Our study demonstrates that the novel Class II HDACI W2 decreases Aβ levelsand improves learning and memory.”
Quote in the paperSubstantial claim
The paper relies on this without support.
HDAC inhibitors alter gene expression epigenetically by interfering with normal HDAC functions.
“Histone deacetylase inhibitors (HDACIs) alter gene expression epigenetically by interfering with the normal functions of HDAC.”
The paper relies on this without support.
Commercially available HDACIs have poor pharmacological properties.
“However, these commercially available HDACIs have poor pharmacological properties.”
The paper relies on this without support.
9-10 month old hAPP 3xTg AD mice exhibit mild cognitive impairment.
“we injected 9-10 month old hAPP 3x Tg AD mice (with mild cognitive impairment) for 4 weeks with W2 (50 mg/kg, daily i.p.) or control.”
The paper relies on this without support.
Findings in mouse models of AD translate to therapeutic benefit in human dementias, including AD.
“Taken together, these data demonstrate that our novel compound Class II HDACI W2 mayhave the potential toalleviatecritical neuropathogenic processes in dementias, including AD, providing broad-spectrum therapeutic benefits.”
The paper relies on this without support.
Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
“Taken together, our data suggest that our novel compounds have dual effects of down-regulating Aβ production pathways while simultaneously up-regulating Aβ clearance mechanisms.”
The paper relies on this without support.
W2 and I2 inhibit HDACs in the tested systems.
“HDAC inhibition decreased expression of genes involved in Aβ production and induced expression of Aβ degradation enzymes.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
HDACI effects on tau phosphorylation described as unknown despite cited prior finding
MinorThe results state that it was unknown whether HDAC inhibitors could alter tau phosphorylation, but the discussion describes a prior HDACI finding that decreased phosphorylated tau at Thr231.
“However, it is unknown whether HDACIs can alter tau phosphorylation.”
“Interestingly, the HDACI nicotinamide increases the level of acetylated α-tubulin, and selectively decreases Thr231-phosphotau in 3x-Tg AD mice (Green, et al., 2008, Hempen and Brion, 1996).”
Cites
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
hnRNP complexes: composition, structure, and function
Krecic, A. M., & Swanson, M. S. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80051-9 · Cited by 813 · see citing works
The secretases: enzymes with therapeutic potential in Alzheimer disease
De Strooper, B., Vassar, R., & Golde, T. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.218 · Cited by 799 · see citing works
Kilgore, M., Miller, C. A., Fass, D. M., Hennig, K. M., Haggarty, S. J., Sweatt, J. D., & Rumbaugh, G. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.197 · Cited by 727 · see citing works
Therapeutic application of histone deacetylase inhibitors for central nervous system disorders
Kazantsev, A. G., & Thompson, L. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2681 · Cited by 715 · see citing works
Govindarajan, N., Agis-Balboa, R. C., Walter, J., Sananbenesi, F., & Fischer, A. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110080 · Cited by 405 · see citing works
Green, K. N., Steffan, J. S., Martinez-Coria, H., Sun, X., Schreiber, S. S., Thompson, L. M., & LaFerla, F. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3203-08.2008 · Cited by 404 · cited 1× · see citing works
“Interestingly, the HDACI nicotinamide increases the level of acetylated α-tubulin, and selectively decreases Thr231-phosphotau in 3xTg AD mice (Green et al., 2008; Hempen and Brion, 1996).”
Temporal Profile of Amyloid-β (Aβ) Oligomerization in an in Vivo Model of Alzheimer Disease
Oddo, S., Caccamo, A., Tran, L., Lambert, M. P., Glabe, C. G., Klein, W. L., & LaFerla, F. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m507892200 · Cited by 379 · see citing works
Qing, H., He, G., Ly, P. T. T., Fox, C. J., Staufenbiel, M., Cai, F., Zhang, Z., Wei, S., Sun, X., Chen, C.-H., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081588 · Cited by 365 · see citing works
Targeting the correct HDAC(s) to treat cognitive disorders
Fischer, A., Sananbenesi, F., Mungenast, A. E., & Tsai, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.003 · Cited by 355 · see citing works
Histone deacetylase inhibitors: discovery and development as anticancer agents
Marks, P. A., & Dokmanovic, M. (2005) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.14.12.1497 · Cited by 318 · see citing works
Ricobaraza, A., Cuadrado‐Tejedor, M., Marco, S., Pérez‐Otaño, I., & García‐Osta, A. (2012) · Hippocampus · doi:10.1002/hipo.20883 · Cited by 239 · see citing works
Hempen, B., & Brion, J. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199609000-00003 · Cited by 177 · see citing works
The Effects of Amyloid Precursor Protein on Postsynaptic Composition and Activity
Hoe, H., Fu, Z., Makarova, A., Lee, J.-Y., Lu, C., Feng, L., Pajoohesh‐Ganji, A., Matsuoka, Y., Hyman, B. T., Ehlers, M., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900141200 · Cited by 114 · see citing works
Self-citationKonsoula, R., & Jung, M. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.05.001 · Cited by 108 · see citing works
Self-citationA G-RICH ELEMENT FORMS A G-QUADRUPLEX AND REGULATES BACE1 mRNA ALTERNATIVE SPLICING
Fisette, J.-F., Montagna, D. R., Mihailescu, M., & Wolfe, M. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07680.x · Cited by 107 · see citing works
BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild‐type mice2
Nishitomi, K., Sakaguchi, G., Horikoshi, Y., Gray, A. J., Maeda, M., Hirata‐Fukae, C., Becker, A. G., Hosono, M., Sakaguchi, I., Minami, S., et al. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04178.x · Cited by 97 · see citing works
Targeting Aβ and tau in Alzheimer's disease, an early interim report
Golde, T. E., Petrucelli, L., & Lewis, J. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2009.07.035 · Cited by 89 · see citing works
Transcriptional dysregulation in a transgenic model of Parkinson disease
Yacoubian, T. A., Cantuti‐Castelvetri, I., Bouzou, B., Asteris, G., McLean, P. J., Hyman, B. T., & Standaert, D. G. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.11.008 · Cited by 66 · see citing works
Long-term Phenylbutyrate administration prevents memory deficits in Tg2576 mice by decreasing A Beta
Garcia-Osta, A. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/e340 · Cited by 50 · see citing works
Kozikowski, A. P., Chen, Y., Tapadar, S., Lewin, N. E., Blumberg, P. M., Zhong, Z., D’Annibale, M. A., Wang, W., Shen, Y., & Langley, B. C. (2009) · ChemMedChem · doi:10.1002/cmdc.200900045 · Cited by 43 · see citing works
Cha, J.-H. J., Farrell, L. A., Ahmed, S. F., Frey, A. S., Ashe, K. H., Young, A. B., Penney, J. B., Locascio, J. J., Hyman, B. T., & Irizarry, M. C. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0330 · Cited by 37 · see citing works
Brain plasticity, memory and neurological disorders: an epigenetic perspective
Lockett, G. A., Wilkes, F., & Maleszka, R. (2010) · Neuroreport · doi:10.1097/wnr.0b013e32833e9288 · Cited by 36 · see citing works
An Alzheimer's disease hypothesis based on transcriptional dysregulation
Robakis, N. K. R. K. (2003) · Amyloid · doi:10.3109/13506120309041729 · Cited by 35 · see citing works
Pharmacological Approaches of Neurofibrillary Degeneration
Iqbal, K., & Grundke, I. (2005) · Current Alzheimer Research · doi:10.2174/1567205054367810 · Cited by 31 · see citing works
Fyn knock-down increases Aβ, decreases phospho-tau, and worsens spatial learning in 3×Tg-AD mice
Minami, S., Clifford, T. G., Hoe, H., Matsuoka, Y., & Rebeck, G. W. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.05.014 · Cited by 28 · see citing works
Self-citationKonsoula, Z., Cao, H., Velena, A., & Jung, M. (2011) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.11.057 · Cited by 27 · see citing works
Self-citationKonsoula, Z., Cao, H., Velena, A., & Jung, M. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0629 · Cited by 27 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Shen, S., & Kozikowski, A. P. (2016) · ChemMedChem · doi:10.1002/cmdc.201500486 · Cited by 288 · see citing works
Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance
Kandlur, A., Satyamoorthy, K., & Gangadharan, G. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00041 · Cited by 177 · see citing works
Jochems, J., Boulden, J., Lee, B. G., Blendy, J. A., Jarpe, M. B., Mazitschek, R., van Duzer, J. H., Jones, S. S., & Berton, O. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.207 · Cited by 168 · see citing works
Yang, S.-S., Zhang, R., Wang, G., & Zhang, Y.-F. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0089-1 · Cited by 163 · see citing works
GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia
Xu, M., & Wong, A. H. C. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.172 · Cited by 159 · see citing works
Recent advances in the discovery of potent and selective HDAC6 inhibitors
Wang, X.-X., Wan, R.-Z., & Liu, Z.-P. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.040 · Cited by 152 · see citing works
Kaminska, B., Mota, M., & Pizzi, M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.026 · Cited by 153 · see citing works
Ganai, S. A., Ramadoss, M., & Mahadevan, V. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666151021111609 · Cited by 155 · see citing works
Histone deacetylases (HDACs) and brain function
Volmar, C.-H., & Wahlestedt, C. (2015) · Neuroepigenetics · doi:10.1016/j.nepig.2014.10.002 · Cited by 151 · see citing works
Bürli, R. W., Luckhurst, C. A., Aziz, O., Matthews, K. L., Yates, D., Lyons, K. A., Beconi, M., McAllister, G., Breccia, P., Stott, A. J., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4011884 · Cited by 153 · see citing works
Cognitive Decline in Preclinical Alzheimer’s Disease: Amyloid-Beta versus Tauopathy
Huber, C. M., Yee, C., May, T., Dhanala, A., & Mitchell, C. S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170490 · Cited by 131 · see citing works
Liu, D., Tang, H., Li, X.-Y., Deng, M.-F., Wei, N., Wang, X., Zhou, Y.-F., Wang, D.-Q., Fu, P., Wang, J.-Z., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.01.018 · Cited by 127 · see citing works
Development and Therapeutic Implications of Selective Histone Deacetylase 6 Inhibitors
Kalin, J. H., & Bergman, J. A. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4001659 · Cited by 129 · see citing works
Wen, K., Milić, J., El‐Khodor, B. F., Dhana, K., Nano, J., Pulido, T., Kraja, B., Začiragić, A., Bramer, W. M., Troup, J., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167201 · Cited by 122 · see citing works
Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease
Maity, S., Farrell, K., Navabpour, S., Narayanan, S. N., & Jarome, T. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212280 · Cited by 123 · see citing works
Zuo, L., Hemmelgarn, B. T., Chuang, C., & Best, T. M. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/604658 · Cited by 118 · see citing works
Alzheimer’s Disorder: Epigenetic Connection and Associated Risk Factors
Sharma, V., Mehta, V., & Singh, T. G. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200128125641 · Cited by 121 · see citing works
Epigenetics: A novel therapeutic approach for the treatment of Alzheimer's disease
Adwan, L. I., & Zawia, N. H. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.03.010 · Cited by 114 · see citing works
The potential of epigenetic therapies in neurodegenerative diseases
Coppedè, F. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00220 · Cited by 114 · see citing works
Epigenetic modifications in the nervous system and their impact upon cognitive impairments
Rudenko, A., & Tsai, L. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.043 · Cited by 108 · see citing works
Luccarini, I., Grossi, C., Rigacci, S., Coppi, E., Pugliese, A. M., Pantano, D., la Marca, G., Dami, T. E., Berti, A., Stefani, M., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.029 · Cited by 112 · see citing works
Epigenetic memory: The Lamarckian brain
Fischer, A. (2014) · The EMBO Journal · doi:10.1002/embj.201387637 · Cited by 107 · see citing works
Fischer, A. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.038 · Cited by 108 · see citing works
Arrazola Sastre, A., Luque Montoro, M., Gálvez-Martín, P., Lacerda, H. M., Lucia, A., Llavero, F., & Zugaza, J. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176312 · Cited by 103 · see citing works
Cuadrado‐Tejedor, M., García, C., Sánchez-Arias, J. A., Rabal, O., Pérez-González, M., Mederos, S., Ugarte, A., Franco, R., Segura, V., Perea, G., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.163 · Cited by 104 · see citing works
HDAC6 in Diseases of Cognition and of Neurons
LoPresti, P. (2020) · Cells · doi:10.3390/cells10010012 · Cited by 105 · see citing works
Epigenetic Basis of Lead-Induced Neurological Disorders
Wang, T., Zhang, J., & Xu, Y. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17134878 · Cited by 98 · see citing works
Neuner, S. M., Wilmott, L. A., Hoffmann, B. R., Mozhui, K., & Kaczorowski, C. C. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.06.002 · Cited by 93 · see citing works
Lu, J., Zhang, H., Chen, X., Zou, Y., Li, J., Wang, L., Wu, M., Zang, J., Yu, Y., Zhuang, W., et al. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.07.012 · Cited by 96 · see citing works
A patent review of histone deacetylase 6 inhibitors in neurodegenerative diseases (2014-2019)
Shen, S., & Kozikowski, A. P. (2019) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2019.1708901 · Cited by 95 · see citing works
Role of Epigenetics in Alzheimer’s Disease Pathogenesis
Stoccoro, A., & Coppedè, F. (2018) · Neurodegenerative Disease Management · doi:10.2217/nmt-2018-0004 · Cited by 90 · see citing works
An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions
Lossi, L., Castagna, C., & Merighi, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073881 · Cited by 99 · see citing works
Rabal, O., Sánchez-Arias, J. A., Cuadrado‐Tejedor, M., de Miguel, I., Pérez-González, M., García, C., Ugarte, A., de Mendoza, A. E., Sáez, E., Espelosin, M., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00908 · Cited by 88 · see citing works
Epigenetic drug discovery for Alzheimer’s disease
Cacabelos, R., & Torrellas, C. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.930124 · Cited by 86 · see citing works
Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease
Cebotaru, L., Liu, Q., Yanda, M. K., Boinot, C., Outeda, P., Huso, D. L., Watnick, T. J., Guggino, W. B., & Cebotaru, V. (2016) · Kidney International · doi:10.1016/j.kint.2016.01.026 · Cited by 87 · see citing works
Early Life Stress and Epigenetics in Late-onset Alzheimer’s Dementia: A Systematic Review
Lemche, E. (2018) · Current Genomics · doi:10.2174/1389202919666171229145156 · Cited by 82 · see citing works
Recent Findings in Alzheimer Disease and Nutrition Focusing on Epigenetics
Athanasopoulos, D., Karagiannis, G., & Tsolaki, M. (2016) · Advances in Nutrition · doi:10.3945/an.116.012229 · Cited by 81 · see citing works
Antisense oligonucleotides for Alzheimer's disease therapy: from the mRNA to miRNA paradigm
Grabowska, W., Want, A., Leszek, J., & Wojda, U. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103691 · Cited by 79 · see citing works
Li, Y., Sang, S., Ren, W., Pei, Y., Bian, Y., Chen, Y., & Sun, H. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113874 · Cited by 77 · see citing works
Cuadrado-Tejedor, M., Garcia-Barroso, C., Sanzhez-Arias, J., Mederos, S., Rabal, O., Ugarte, A., Franco, R., Pascual-Lucas, M., Segura, V., Perea, G., et al. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0142-9 · Cited by 69 · see citing works
Stolfa, D. A., Marek, M., Lancelot, J., Hauser, A.-T., Walter, A., Leproult, E., Melesina, J., Rumpf, T., Wurtz, J.-M., Cavarelli, J., et al. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.03.007 · Cited by 75 · see citing works
Self-citationEpigenetic Modifications in Alzheimer’s Neuropathology and Therapeutics
Esposito, M. M., & Sherr, G. L. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00476 · Cited by 67 · see citing works
Rabal, O., Sánchez-Arias, J. A., Cuadrado‐Tejedor, M., de Miguel, I., Pérez-González, M., García, C., Ugarte, A., de Mendoza, A. E., Sáez, E., Espelosin, M., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.03.005 · Cited by 71 · see citing works
Teijido, Ó., & Cacabelos, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103199 · Cited by 68 · see citing works
Nagu, P., Parashar, A., Behl, T., & Mehta, V. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01829-3 · Cited by 64 · see citing works
Volmar, C., Salah-Uddin, H., Janczura, K. J., Halley, P., Lambert, G., Wodrich, A. P. K., Manoah, S., Patel, N. H., Sartor, G. C., Mehta, N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707544114 · Cited by 64 · see citing works
Majid, T., Griffin, D. M., Criss, Z. K., Jarpe, M. B., & Pautler, R. G. (2015) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2015.08.001 · Cited by 60 · see citing works
Cao, T., Zhou, X., Zheng, X., Cui, Y., Tsien, J. Z., Li, C., & Wang, H. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00137 · Cited by 61 · see citing works
Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases
Irwin, M. H., Moos, W. H., Faller, D. V., Steliou, K., & Pinkert, C. A. (2016) · Drug Development Research · doi:10.1002/ddr.21294 · Cited by 56 · see citing works
Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration
Jiang, D., Li, T., Guo, C., Tang, T.-S., & Liu, H. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-00953-4 · Cited by 54 · see citing works
Hsu, K., Liu, C., Lin, T. E., Hsieh, J.-H., Sung, T.-Y., Tseng, H.-J., Yang, J., & Huang, W. (2017) · Scientific Reports · doi:10.1038/s41598-017-03417-1 · Cited by 54 · see citing works
Emerging drug targets for A β and tau in Alzheimer's disease: a systematic review
West, S., & Bhugra, P. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12621 · Cited by 50 · see citing works
Histone Deacetylase Inhibitors: A Therapeutic Key in Neurological Disorders?
Ziemka‐Nałęcz, M., Jaworska, J., Sypecka, J., & Zalewska, T. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly073 · Cited by 50 · see citing works
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia
Agís‐Balboa, R. C., Pinheiro, P. S., Rebola, N., Kerimoglu, C., Benito, E., Gertig, M., Bahari‐Javan, S., Jain, G., Burkhardt, S., Delalle, I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796821 · Cited by 49 · see citing works
Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease
Xiao, X., Liu, X., & Jiao, B. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.538301 · Cited by 49 · see citing works
Guo, S., Zhen, Y., Zhu, Z., Zhou, G., & Zheng, X. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116819 · Cited by 49 · see citing works
The Contribution and Therapeutic Potential of Epigenetic Modifications in Alzheimer’s Disease
Wood, I. C. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00649 · Cited by 43 · see citing works
Cuadrado‐Tejedor, M., Pérez-González, M., García‐Muñoz, C., Muruzabal, D., García, C., Rabal, O., Segura, V., Sánchez-Arias, J. A., Oyarzábal, J., & García‐Osta, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00149 · Cited by 45 · see citing works
Tavares, M. T., Kozikowski, A. P., & Shen, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112887 · Cited by 52 · see citing works
Amin, S. A., Adhikari, N., Kotagiri, S., Jha, T., & Ghosh, B. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.01.077 · Cited by 44 · see citing works
Noh, H., & Seo, H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.012 · Cited by 41 · see citing works
Histone-acetylation: a link between Alzheimer's disease and post-traumatic stress disorder?
Bahari‐Javan, S., Sananbenesi, F., & Fischer, A. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00160 · Cited by 41 · see citing works
Segretti, M. C. F., Vallerini, G. P., Brochier, C., Langley, B. C., Wang, L., Hancock, W. W., & Kozikowski, A. P. (2015) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00303 · Cited by 42 · see citing works
Rabal, O., Sánchez-Arias, J. A., Cuadrado‐Tejedor, M., de Miguel, I., Pérez-González, M., García, C., Ugarte, A., de Mendoza, A. E., Sáez, E., Espelosin, M., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00303 · Cited by 46 · see citing works
Lardenoije, R., van den Hove, D., Havermans, M., van Casteren, A., Le, K. X., Palmour, R., Lemere, C. A., & Rutten, B. P. F. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.11.002 · Cited by 42 · see citing works
Celen, S., Rokka, J., Gilbert, T. M., Koole, M. J. B., Vermeulen, I., Serdons, K., Schroeder, F. A., Wagner, F. F., Bleeser, T., Hightower, B. G., et al. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00074 · Cited by 40 · see citing works
Li, G., Kim, C., Kim, J., Yoon, H., Zhou, H., & Kim, J. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150024 · Cited by 39 · see citing works
Self-citationGlial epigenetics in neuroinflammation and neurodegeneration
Staszewski, O., & Prinz, M. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1815-y · Cited by 38 · see citing works
Epigenetic drugs in Alzheimer’s disease
Cuadrado‐Tejedor, M., Oyarzábal, J., Pascual‐Lucas, M., Franco, R., & García‐Osta, A. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2013-0012 · Cited by 37 · see citing works
Epigenetic suppression of hippocampal BDNF mediates the memory deficiency induced by amyloid fibrils
Wang, B., Zhong, Y., Zhao, Z., & Miao, Y. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.09.009 · Cited by 36 · see citing works
Yanda, M. K., Liu, Q., & Cebotaru, L. (2017) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00186.2017 · Cited by 35 · see citing works
Epigenetic basis of Alzheimer disease
Tecalco-Cruz, Á. C., Ramírez‐Jarquín, J. O., Álvarez-Sánchez, M. E., & Zepeda–Cervantes, J. (2020) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v11.i2.62 · Cited by 37 · see citing works
Neurogenesis-based epigenetic therapeutics for Alzheimer's disease (Review)
Li, X., Bao, X., & Wang, R. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5390 · Cited by 34 · see citing works
Sánchez-Arias, J. A., Rabal, O., Cuadrado‐Tejedor, M., de Miguel, I., Pérez-González, M., Ugarte, A., Sáez, E., Espelosin, M., Ursúa, S., Haizhong, T., et al. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00370 · Cited by 35 · see citing works
Dubey, H., Gulati, K., & Ray, A. (2018) · NeuroToxicology · doi:10.1016/j.neuro.2018.03.001 · Cited by 32 · see citing works
Clinical validation of the novel HDAC6 radiotracer [18F]EKZ-001 in the human brain
Koole, M. J. B., Weehaeghe, D. V., Serdons, K., Herbots, M., Cawthorne, C., Celen, S., Schroeder, F. A., Hooker, J. M., Bormans, G. M., Hoon, J. N. J. M. D., et al. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-04891-y · Cited by 33 · see citing works
Alzheimer’s Disease-Related Epigenetic Changes: Novel Therapeutic Targets
Paniri, A., Hosseini, M. M., & Akhavan‐Niaki, H. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03626-y · Cited by 32 · see citing works
He, F., Ran, Y., Li, X., Wang, D., Zhang, Q., Lv, J., Yu, C., Qu, Y., Zhang, X., Xu, A., et al. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104109 · Cited by 31 · see citing works
Drugging the Schistosome Zinc-Dependent HDACs: Current Progress and Future Perspectives
Marek, M., Oliveira, G., Pierce, R. J., Jung, M., Sippl, W., & Romier, C. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.25 · Cited by 30 · see citing works
Self-citationHistone deacetylase in neuropathology
Gupta, R. V., Ambasta, R. K., & Kumar, P. (2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2020.09.004 · Cited by 28 · see citing works
Nuclear dynamics and stress responses in Alzheimer’s disease
Iatrou, A., Clark, E. M., & Wang, Y. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00489-6 · Cited by 27 · see citing works
Discovery of a fluorescent probe with HDAC6 selective inhibition
Zhang, Y., Jin, Y., & Yao, T. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.022 · Cited by 28 · see citing works
Muscone Ameliorates Synaptic Dysfunction and Cognitive Deficits in APP/PS1 Mice
Liu, Y., Bian, H., Xu, S., Shu, S., Jia, J., Chen, J., Cao, X., Bao, X., Gu, Y., Xia, S., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200188 · Cited by 25 · see citing works
Alzheimer’s Disease: the Potential of Epigenetic Treatments and Current Clinical Candidates
Coneys, R., & Wood, I. C. (2020) · Neurodegenerative Disease Management · doi:10.2217/nmt-2019-0034 · Cited by 26 · see citing works
Mendelian, Non-Mendelian, Multigenic Inheritance, and Epigenetics
Harel, T., Pehli̇van, D., Caskey, C. T., & Lupski, J. R. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-410529-4.00001-2 · Cited by 26 · see citing works
Epigenetic modulation of Cdk5 contributes to memory deficiency induced by amyloid fibrils
Li, L., Zhang, C.-Q., Zi, X., Tu, Q., & Guo, K. (2014) · Experimental Brain Research · doi:10.1007/s00221-014-4100-0 · Cited by 18 · see citing works
Wang, X.-X., Xie, F., Jia, C.-C., Yan, N., Zeng, Y.-L., Wu, J.-D., & Liu, Z.-P. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113821 · Cited by 23 · see citing works
Epigenetic regulation of synaptic disorder in Alzheimer’s disease
Chen, Z., Wu, M., Lai, Q., Zhou, W., Wen, X., & Yin, X. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.888014 · Cited by 21 · see citing works
HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease
Diniz, L. P., Pinheiro, P. D. S. M., Franco, L. S., & Gomes, F. C. A. (2025) · Cells · doi:10.3390/cells14171338 · Cited by 26 · see citing works
Gupta, R. V., Ambasta, R. K., & Kumar, P. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117912 · Cited by 20 · see citing works
Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue
Janowski, M., Milewska, M., Zare, P., & Pękowska, A. (2021) · Pharmaceuticals · doi:10.3390/ph14080765 · Cited by 21 · see citing works
Hung, T.-C., Lee, W., Chen, K., Chan, Y.-C., Lee, C.-C., & Chen, C. Y. (2014) · BioMed Research International · doi:10.1155/2014/769867 · Cited by 19 · see citing works
Song, J. M., Sung, Y. M., Nam, J. H., Yoon, H., Chung, A., Moffat, E., Jung, M., Pak, D. T. S., Kim, J., & Hoe, H.-S. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150717 · Cited by 18 · see citing works
Self-citationEpigenetics in Alzheimer’s Disease: A Critical Overview
Villa, C., & Combi, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115970 · Cited by 18 · see citing works
Almaguer, J., Hindle, A., & Lawrence, J. J. (2023) · Antioxidants · doi:10.3390/antiox12111921 · Cited by 19 · see citing works
Nakatsuka, D., Izumi, T., Tsukamoto, T., Oyama, M., Nishitomi, K., Deguchi, Y., Niidome, K., Yamakawa, H., Ito, H., & Ogawa, K. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.782375 · Cited by 15 · see citing works
Histone deacetylase inhibitor attenuates neurotoxicity of clioquinol in PC12 cells
Fukui, T., Asakura, K., Hikichi, C., Ishikawa, T., Murai, R., Hirota, S., Murate, K., Kizawa, M., Ueda, A., Ito, S., et al. (2015) · Toxicology · doi:10.1016/j.tox.2015.01.013 · Cited by 15 · see citing works
Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors
Faridoon, Zha, Y. L., Zhang, G., & Li, J. J. (2022) · Medicinal Chemistry Research · doi:10.1007/s00044-022-02987-8 · Cited by 19 · see citing works
Epigenetic Drug Discovery for Alzheimer’s Disease
Cacabelos, R., & Teijido, Ó. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-811060-7.00022-x · Cited by 14 · see citing works
Fang, Y., Hsieh, J., Vidyanti, A. N., Yang, C., Jan, J., Chang, K., Hu, C., & Tu, Y. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16770 · Cited by 14 · see citing works
- Authors
- Sung, Y. M., Lee, T., Yoon, H., DiBattista, A. M., Song, J. M., Sohn, Y., Moffat, E. I., Turner, R. S., Jung, M., Kim, J., & Hoe, H.-S.
- Affiliations
- Seoul National University (KR)
- Georgetown University Medical Center (US)
- Washington University in St. Louis (US)
- Corresponding author
- Kim, Jungsu
- Hoe, Hyang-Sook
- ORCID
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 239
- Pages
- 192-201
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC3780389
- OpenAlex
- W2080228122
- Semantic Scholar
- a4fe4e1e74beffa979069b353f236ca4c18a51bb
- Cited by
- 137
- References
- 28
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 19 · 2019: 7 · 2018: 9 · 2017: 14 · 2016: 11 · 2015: 14 · 2014: 16 · 2013: 7
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- NIH (AG034253, AG039708, AG026478, P30NS069329)
- M4M Recipient of Young investigator award
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- histone deacetylase inhibitors, Alzheimer's disease, amyloid-beta, gamma-secretase, MMP-2, learning and memory, tau phosphorylation, blood-brain barrier penetration, epigenetic therapy
- MeSH terms
- Acetamides, Alzheimer Disease, Animals, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Humans, Learning, Memory, Mice, Transgenic, Microinjections, Neurons, Phosphorylation, Thioglycolates, Transfection, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Maze Learning, Mice, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Real-Time Polymerase Chain Reaction
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-17.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-17.
Cited sources are checked by gpt-6-sol.
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 ›
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