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Roflumilast, a Phosphodiesterase-4 Inhibitor, Ameliorates Sleep Deprivation-Induced Cognitive Dysfunction in C57BL/6J Mice

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Moderate-Intensity Intermittent Training Alters the DNA Methylation Pattern of PDE4D Gene in Hippocampus to Improve the Ability of Spatial Learning and Memory in Aging Rats Reduced by D-Galactose

Zhang, J., Gao, Q., Gao, J., Lv, L., Liu, R., Wu, Y., Li, X., Jin, Y., & Wang, L. (2023) · Brain Sciences · doi:10.3390/brainsci13030422 · Cited by 18 · see citing works

Roflumilast and cognition enhancement: A translational perspective

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Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement

Wei, X., Yu, G., Shen, H., Luo, Y., Shang, T., Shen, R., Xi, M., & Sun, H. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106278 · Cited by 17 · see citing works

Roflumilast ameliorates ovariectomy-induced depressive-like behavior in rats via activation of AMPK/mTOR/ULK1-dependent autophagy pathway

Zaki, E. S., Sayed, R. H., Saad, M. A., & El-Yamany, M. F. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121806 · Cited by 17 · see citing works

The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression

Li, X., Li, J., Huang, Y., Gong, Q., Fu, Y., Xu, Y., Huang, J., You, H., Zhang, D., Zhang, D., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.114045 · Cited by 16 · see citing works

Intermittent treatment with Apremilast, a phosphodiesterase-4 inhibitor, ameliorates Alzheimer's-like pathology and symptoms through multiple targeting actions in aged T2D rats

Gomaa, A. A., Farghaly, H. S. M., Ahmed, A. M., & Hemida, F. K. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109927 · Cited by 16 · see citing works

Arrestin-dependent nuclear export of phosphodiesterase 4D promotes GPCR-induced nuclear cAMP signaling required for learning and memory

Martinez, J. M., Shen, A., Xu, B. Y., Jovanović, A., de Chabot, J., Zhang, J., & Xiang, Y. K. (2023) · Science Signaling · doi:10.1126/scisignal.ade3380 · Cited by 15 · see citing works

Upregulation of Phosphodiesterase 7A Contributes to Concurrent Pain and Depression via Inhibition of cAMP-PKA-CREB-BDNF Signaling and Neuroinflammation in the Hippocampus of Mice

Chen, S., Chen, Y., Song, Y., Zong, S.-H., Wu, M., Wang, W., Wang, H., Zhang, F., Yan-meng, Z., Yu, H., et al. (2024) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyae040 · Cited by 13 · see citing works

Roflumilast, a cyclic nucleotide phosphodiesterase 4 inhibitor, protects against cerebrovascular endothelial injury following cerebral ischemia/reperfusion by activating the Notch1/Hes1 pathway

Cai, N., Xu, B., Li, X., Qin, Y., Li, M., Chen, K., Xu, J., & Wang, H. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175027 · Cited by 13 · see citing works

Unraveling the Potential Underlying Mechanisms of Mild Behavioral Impairment: Focusing on Amyloid and Tau Pathology

Angelopoulou, E., Bougea, A. M., Hatzimanolis, A., Scarmeas, N., & Papageorgiou, S. G. (2024) · Cells · doi:10.3390/cells13131164 · Cited by 14 · see citing works

Selective Inhibition of PDE4B Reduces Methamphetamine Reinforcement in Two C57BL/6 Substrains

Honeywell, K. M., Doren, E. V., & Szumlinski, K. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094872 · Cited by 12 · see citing works

Long-term treatment with roflumilast improves learning of fear extinction memory and anxiety-like response in a type-1 diabetes mellitus animal model

Waltrick, A. P. F., da Silva, A. C. F., de Mattos, B. A., Chaves, Y. C., de Oliveira, R. M. W., Prickaerts, J., & Zanoveli, J. M. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.114217 · Cited by 11 · see citing works

Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders

Park, M. K., Yang, H. W., Woo, S. Y., Kim, D., Son, D., Choi, B. Y., & Suh, S. W. (2025) · Cells · doi:10.3390/cells14020086 · Cited by 11 · see citing works

The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice

Wang, L., Li, M., Zhu, C., Qin, A., Wang, J., & Wei, X. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03672-3 · Cited by 11 · see citing works

Roflumilast attenuates doxorubicin and cyclophosphamide combination-induced chemobrain in rats through modulation of NLRP3/ASC/caspase-1/GSDMD axis

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Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer’s Disease

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Dual PDE4/10A inhibition restores CREB1 function and enhances neuronal resilience in models of alzheimer's disease

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Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors

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Characterization of Resveratrol, Oxyresveratrol, Piceatannol and Roflumilast as Modulators of Phosphodiesterase Activity. Study of Yeast Lifespan

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Apoptosis in health and diseases of the eye and brain

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Suppression of phosphodiesterase IV enzyme by roflumilast ameliorates cognitive dysfunction in aged rats after sevoflurane anaesthesia via PKA‐CREB and MEK/ERK pathways

Liu, P., Wang, J., Peng, S., Zhang, D., Zhuang, L., Liu, C., Zhang, Y., & Shi, X. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15751 · Cited by 10 · see citing works

Influence of smoke suppressant on the smoke inhibition effect and properties of different types of asphalt

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Pharmacologic treatment of depression in Alzheimer’s disease

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Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis

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Cognitive improvement effects of PF-04957325, a phosphodiesterase-8 inhibitor, in mouse models of Alzheimer’s disease via modulating neuroinflammation

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Inhibition of phosphodiesterase 4 attenuates aquaporin 4 expression and astrocyte swelling following cerebral ischemia/reperfusion injury

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Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease

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Protective mechanism of the EZH2/microRNA-15a-5p/CXCL10 axis in rats with depressive-like behaviors

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Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer’s Disease

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Phosphodiesterase 4 inhibition after retrieval switches the memory fate favoring extinction instead of reconsolidation

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Blood–Brain Barrier Rescue by Roflumilast After Transient Global Cerebral Ischemia in Rats

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A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats

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Recent development in PDE4D-targeted inhibitors for Alzheimer's disease therapy

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Chronic pain exacerbates memory impairment and pathology of Aβ and tau by upregulating IL-1β and p-65 signaling in a mouse model of Alzheimer’s disease

Wang, W., Zheng, W.-Q., Du, X., Chen, S.-C., Chen, Y., Ma, Q.-Y., Wang, H., Gao, S., Tan, R., Zhang, H., et al. (2024) · Brain Research · doi:10.1016/j.brainres.2024.148843 · Cited by 5 · see citing works

Discovery of α-mangostin derivatives as novel PDE4 inhibitors for the treatment of Alzheimer's disease: An artificial intelligence-driven synergized strategy

Sang, Z., Xue, T., Xing, Q.-R., Zhang, Q.-Y., Chen, H., Wang, X., Zhang, F., Fu, W.-L., Dong, W., Huang, S., et al. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.111318 · Cited by 4 · see citing works

Efficacy of Piper Longum Extract in a Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease Combined with Chronic Restraint Through Lipocalin-2-Associated Neuroinflammatory Mechanism

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Phosphodiesterase 4 (PDE4) and neurological disorders: A promising frontier in neuropharmacology

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Investigation of apoptotic and autophagic effects of chronic roflumilast use on testicular tissue in rats by immunohistochemical and immunofluorescence methods.

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Beta‐amyloid interacts with and activates the long‐form phosphodiesterase PDE4D5 in neuronal cells to reduce cAMP availability

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Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases

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Correlation of autophagy and Alzheimer's disease with special emphasis on the role of phosphodiesterase-4

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High throughput mRNA sequencing reveals potential therapeutic targets of Si-Ni-San in the pons for a stress-induced depression model

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Phosphodiesterase-4 Inhibition: An Experimental Approach to Overcome Drug Resistance in a Rotenone-Corneal 6 Hz Kindling Mouse Model of Drug-Resistant Epilepsy

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Effect and mechanism of maternal prolactin levels on depressive-like behavior in prenatally stressed offspring

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Modulation of cognitive activity by plant-based extracts (Allium cepa, Coffea robusta, and Brassica oleracea) through the phosphodiesterase 4B inhibition: Insite from a Mice model study

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f-MRI and High Throughput mRNA sequencing reveals potenti-al therapeutic targets of Si-Ni-San in a stress-induced depressionmodelPreprint

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Picking the best isoform

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Discovery of a novel PDE4 inhibitor with dibenzofuran moiety from marine fungal metabolites for Alzheimer's disease therapy

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Unveiling Remyelinating Properties of Roflumilast in CPZ‐Induced Neuronal Demyelination in Mice

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Repurposing apremilast for alzheimer’s disease: multitarget modulation of cAMP‑PI3K/Akt–GSK‑3β and NF‑κB signaling

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Dissecting the shared genetic architecture and biological mechanisms linking sleep traits and suicide attempts: from variants to genes

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BindingDB (2023) · UC San Diego · doi:10.7270/q29k4g4c

BindingDB Entry 50022452: Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors.

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Roflumilast ameliorates cognitive impairment in APP/PS1 mice via cAMP/CREB/BDNF signaling and anti-neuroinflammatory effects

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Inhibition of phosphodiesterase‐4D reverses memory deficits and depression‐like effects via cAMP signaling in mouse models of Alzheimer's disease

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Rolipram Ameliorates Memory Deficits and Depression-Like Behavior in APP/PS1/tau Triple Transgenic Mice: Involvement of Neuroinflammation and Apoptosis via cAMP Signaling

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FFPM, a PDE4 inhibitor, reverses learning and memory deficits in APP/PS1 transgenic mice via cAMP/PKA/CREB signaling and anti-inflammatory effects

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