Roflumilast: A potential drug for the treatment of cognitive impairment?
Abstract
Phosphodiesterase-4 regulates the intracellular level of cAMP. Roflumilast, a selective PDE-4 inhibitor was the first agent in this class to have reached the market for patients with chronic obstructive pulmonary disease worldwide. Numerous preclinical evidences indicate the role of PDE-4 inhibitors in reversal of ageing-related alterations induced in animal models by various pharmacological agents, overexpression of mutant forms of human amyloid precursor proteins and in aging, as well. Roflumilast was capable of decreasing PDE-4B and 4D subtypes with an increase in the expression of pCREB and BDNF in hippocampus of rats. The beneficial effects of roflumilast on cognition are believed to be mediated through the above-mentioned cellular effects. Recently, Jabaris et al had shown that roflumilast has improved the short and long-term memory in rodents. Several lines of evidence indicate that targeting PDE-4 inhibition might offer novel approaches in the treatment of age-associated memory impairment and in Alzheimer's disease. Likewise, in a recent report, roflumilast improved the memory functions in humans after administration of 100 μg of the drug, without the typical side effects of PDE-4 inhibitors, which might offer a novel therapeutic option for the treatment of cognitive impairment and Alzheimer disease. In the current article, the author reviews the most recent evidences demonstrating the beneficial effects of roflumilast on learning and memory in animal models and humans.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
PDE4 inhibitors include roflumilast, an oral small compound that selectively inhibits PDE4, an enzyme involved in controlling cAMP levels, and may lessen inflammation and increase neuronal survival.
“PDE4 inhibitors, which are oral small compounds that selectively inhibit PDE4, an enzyme involved in controlling cAMP levels, include roflumilast (15, Figure 5), which may lessen inflammation and increase neuronal survival [177,178,179,180].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [178]
Cites
Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
Calverley, P. M. A., Rabe, K. F., Goehring, U.-M., Kristiansen, S., Fabbri, L. M., & Martínez, F. J. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61255-1 · Cited by 821 · see citing works
Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues
Lakics, V., Karran, E. H., & Boess, F. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.05.004 · Cited by 468 · see citing works
Burgin, A. B., Magnússon, Ó. Þ., Singh, J., Witte, P., Staker, B. L., Björnsson, J. M., Þorsteinsdóttir, M., Hrafnsdóttir, S., Hagen, T. J., Kiselyov, A. S., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1598 · Cited by 396 · see citing works
Phosphodiesterases in the CNS: targets for drug development
Menniti, F. S., Faraci, W. S., & Schmidt, C. J. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2058 · Cited by 391 · see citing works
Jin, S.-L. C., & Conti, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122041599 · Cited by 368 · see citing works
Effect of 1-Year Treatment with Roflumilast in Severe Chronic Obstructive Pulmonary Disease
Calverley, P. M. A., Sánchez-Toril, F., McIvor, A., Teichmann, P., Bredenbroeker, D., & Fabbri, L. M. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200610-1563oc · Cited by 324 · see citing works
Rabe, K. F. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01218.x · Cited by 272 · see citing works
Selective phosphodiesterase inhibitors: a promising target for cognition enhancement
Reneerkens, O. A. H., Rutten, K., Steinbusch, H. W. M., Blokland, A., & Prickaerts, J. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1273-x · Cited by 268 · see citing works
Phosphodiesterases as Therapeutic Targets for Alzheimer's Disease
García‐Osta, A., Cuadrado‐Tejedor, M., García, C., Oyarzábal, J., & Franco, R. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn3000907 · Cited by 260 · see citing works
Li, Y., Cheng, Y., Huang, Y., Conti, M., Wilson, S. P., O’Donnell, J. M., & Zhang, H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5236-10.2011 · Cited by 233 · see citing works
Pérez-Torres, S., Miró, X., Palacios, J. M., Cortés, R., Puigdomènech, P., & Mengod, G. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00097-1 · Cited by 231 · see citing works
Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)
Zhang, H., Huang, Y., Masood, A., Stolinski, L. R., Li, Y., Zhang, L., Dlaboga, D., Jin, S.-L. C., Conti, M., & O’Donnell, J. M. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301537 · Cited by 180 · see citing works
Prickaerts, J., Heckman, P. R. A., & Blokland, A. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1364360 · Cited by 172 · see citing works
Roflumilast: a review of its use in the treatment of COPD
Wedzicha, J., Calverley, P., & Rabe, K. (2016) · International Journal of COPD · doi:10.2147/copd.s89849 · Cited by 168 · see citing works
Wang, C., Yang, X., Zhuo, Y., Zhou, H., Lin, H.-B., Cheng, Y., Xu, J., & Zhang, H. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000836 · Cited by 150 · see citing works
PDE4 as a target for cognition enhancement
Richter, W., Menniti, F. S., Zhang, H., & Conti, M. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.818656 · Cited by 148 · see citing works
GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses
Bruno, O., Fedele, E., Prickaerts, J., Parker, L. A., Canepa, E., Brullo, C., Cavallero, A., Gardella, E., Balbi, A., Domenicotti, C., et al. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01524.x · Cited by 137 · see citing works
Zhang, H., & O’Donnell, J. M. (2000) · Psychopharmacology · doi:10.1007/s002130000414 · Cited by 136 · see citing works
Roflumilast: a review of its use in the treatment of COPD
Wedzicha, J. A., Calverley, P. M. A., & Rabe, K. F. (2016) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 124 · see citing works
Inhaled Phosphodiesterase 4 (PDE4) Inhibitors for Inflammatory Respiratory Diseases
Phillips, J. E. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00259 · Cited by 119 · see citing works
The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses
Vanmierlo, T., Creemers, P., Akkerman, S., van Duinen, M. A., Sambeth, A., Vry, J. D., Uz, T., Blokland, A., & Prickaerts, J. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.01.031 · Cited by 112 · see citing works
The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro
Jones, N. A., Boswell‐Smith, V., Lever, R., & Page, C. P. (2004) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2004.10.001 · Cited by 100 · see citing works
Targeting CREB signalling in neurogenesis
Dworkin, S., & Mantamadiotis, T. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.501332 · Cited by 96 · see citing works
Giembycz, M. A. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.297 · Cited by 92 · see citing works
Treating COPD with PDE 4 inhibitors.
Brown, W. M. (2007) · PubMed Central · Cited by 78 · see citing works
PDE4: A Novel Target in the Treatment of Chronic Obstructive Pulmonary Disease
Michalski, J., Golden, G. A., Ikari, J., & Rennard, S. I. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.266 · Cited by 78 · see citing works
Ricciarelli, R., Brullo, C., Prickaerts, J., Arancio, O., Villa, C., Rebosio, C., Calcagno, E., Balbi, M., van Hagen, B. T. J., Argyrousi, E. K., et al. (2017) · Scientific Reports · doi:10.1038/srep46320 · Cited by 78 · see citing works
Nagakura, A., Niimura, M., & Takeo, S. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704629 · Cited by 76 · see citing works
Feng, H., Wang, C., He, W., Wu, X.-J., Li, S., Zeng, Z., Wei, M., & He, B. (2019) · Metabolic Brain Disease · doi:10.1007/s11011-018-0374-4 · Cited by 72 · see citing works
Drug safety evaluation of roflumilast for the treatment of COPD: a meta-analysis
Rogliani, P., Calzetta, L., Cazzola, M., & Matera, M. G. (2016) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2016.1199683 · Cited by 66 · see citing works
van Duinen, M. A., Sambeth, A., Heckman, P. R. A., de Smit, S., Tsai, M., Lahu, G., Uz, T., Blokland, A., & Prickaerts, J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.12.019 · Cited by 63 · see citing works
Liu, S., Veilleux, A., Zhang, L., Young, A. J., Kwok, E., Laliberté, F., Chung, C., Tota, M. R., Dubé, D., Friesen, R. W., et al. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.083519 · Cited by 59 · see citing works
Benefits and harms of roflumilast in moderate to severe COPD
Yu, T., Fain, K. M., Boyd, C. M., Singh, S., Weiss, C. O., Li, T., Varadhan, R., & Puhan, M. A. (2013) · Thorax · doi:10.1136/thoraxjnl-2013-204155 · Cited by 55 · see citing works
Hu, J., Pan, T., An, B., Li, Z., Li, X., & Huang, L. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.12.013 · Cited by 53 · see citing works
Rutter, A. R., Poffe, A., Cavallini, P., Davis, T. G., Schneck, J. L., Negri, M., Vicentini, E., Montanari, D., Arban, R., Gray, F. A., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.214155 · Cited by 52 · see citing works
Santiago, A. N., Soares, L. M., Schepers, M., Milani, H., Vanmierlo, T., Prickaerts, J., & de Oliveira, R. M. W. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.06.019 · Cited by 49 · see citing works
Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice
Udalov, S., Dumitrascu, R., Pullamsetti, S. S., Al-tamari, H. M., Weißmann, N., Ghofrani, H. A., Günther, A., Voswinckel, R., Seeger, W., Grimminger, F., et al. (2010) · BMC Pulmonary Medicine · doi:10.1186/1471-2466-10-26 · Cited by 47 · see citing works
Sugin Lal Jabaris, S., Sumathy, H., Kumar, R. S., Narayanan, S., Thanikachalam, S., & Chidambaram, S. B. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.10.039 · Cited by 47 · see citing works
The cAMP-specific phosphodiesterase 4B mediates Aβ-induced microglial activation
Sebastiani, G., Morissette, C., Lagacé, C., Boulé, M., Ouellette, M., McLaughlin, R. W., Lacombe, D., Gervais, F., & Tremblay, P. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.024 · Cited by 44 · see citing works
Sub-chronic rolipram treatment leads to a persistent improvement in long-term object memory in rats
Rutten, K., Prickaerts, J., Schänzle, G., Rosenbrock, H., & Blokland, A. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.04.016 · Cited by 41 · see citing works
Brullo, C., Ricciarelli, R., Prickaerts, J., Arancio, O., Massa, M., Rotolo, C., Romussi, A., Rebosio, C., Marengo, B., Pronzato, M. A., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.08.018 · Cited by 39 · see citing works
Sharma, V., Bala, A., Deshmukh, R. R., Bedi, K. L., & Sharma, P. L. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.01.004 · Cited by 38 · see citing works
Bian, H., Zhang, J., Wu, P., Varty, L. M., Jia, Y., Mayhood, T., Hey, J. A., & Wang, P. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.08.014 · Cited by 34 · see citing works
Sugin Lal Jabaris, S., Sumathy, H., Girish, R., Narayanan, S., Sugumar, M., Babu, C. S., Thanikachalam, S., & Thanikachalam, M. (2015) · Brain Research · doi:10.1016/j.brainres.2015.07.003 · Cited by 33 · see citing works
Zhang, M.-Z., Zhou, Z., Yuan, X., Cheng, Y., Bi, B., Gong, M., Chen, Y.-P., & Xu, J. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.09.055 · Cited by 33 · see citing works
The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice
Liu, X. B., Hao, P., Yang, M., Sun, J., Mao, L., Fan, C., Zhang, Z., Li, D.-W., Yang, X., Sun, B., et al. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4631-8 · Cited by 32 · see citing works
Huang, Z., Dias, R., Jones, T. R., Liu, S., Styhler, A., Claveau, D., Otu, F., Ng, K., Laliberté, F., Zhang, L., et al. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.03.010 · Cited by 30 · see citing works
Sensory Gating in Patients With Alzheimer’s Disease and Their Biological Children
Ally, B. A., Jones, G. E., Cole, J. A., & Budson, A. E. (2007) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317506292282 · Cited by 28 · see citing works
Yeo, C. D., Kim, Y. A., Lee, H. Y., Kim, J. W., Kim, S. J., Lee, S. H., & Kim, Y. K. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.07.004 · Cited by 25 · see citing works
Peng, S., Yan, H., Liu, P., Shi, X., Liu, C., Liu, Q., & Zhang, Y. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000488180 · Cited by 23 · see citing works
Heckman, P. R. A., van Duinen, M. A., Blokland, A., Uz, T., Prickaerts, J., & Sambeth, A. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4770-y · Cited by 18 · see citing works
Takano, A., Uz, T., Garcia‐Segovia, J., Tsai, M. C., Lahu, G., Amini, N., Nakao, R., Jia, Z., & Halldin, C. (2018) · Molecular Imaging and Biology · doi:10.1007/s11307-018-1168-0 · Cited by 17 · see citing works
Roflumilast attenuates cognitive deficits in estrogen insufficient rats
Goyal, A., & Garabadu, D. (2020) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000574 · Cited by 8 · see citing works
The PDE4-inhibitor roflumilast improves memory: findings from a translational perspective
van Duinen, M. A., Sambeth, A., Heckman, P. R. A., Tsai, M., Lahu, G., Uz, T., Blokland, A., & Prickaerts, J. (2017) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(17)31794-7 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 55 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56 · see citing works
The role of inflammation in cadmium nephrotoxicity: NF-κB comes into view
Hassanein, E. H. M., Mohamed, W. R., Ahmed, O. S., Abdel‐Daim, M. M., & Sayed, A. M. M. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120971 · Cited by 48 · see citing works
Donders, Z., Skorupska, I. J., Willems, E., Mussen, F., Broeckhoven, J. V., Carlier, A., Schepers, M., & Vanmierlo, T. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117009 · Cited by 39 · see citing works
Pharmacotherapies in Older Adults with COPD: Challenges and Opportunities
Matera, M. G., Hanania, N. A., Maniscalco, M., & Cazzola, M. (2023) · Drugs & Aging · doi:10.1007/s40266-023-01038-0 · Cited by 33 · see citing works
“It must be mentioned that much preclinical evidence points to the function of phosphodiesterase 4 inhibitors in the restoration of agingrelated changes generated in animal models by various pharmacological agents and in the overexpression of mutant versions of human amyloid precursor proteins and aging [52].”
BackgroundPharmacological Strategies to Improve Dendritic Spines in Alzheimer’s Disease
Ettcheto, M., Busquets, O., Cano, A. C., Sánchez‐López, E., Manzine, P. R., Espinosa-Jiménez, T., Verdaguer, E., Sureda, F. X., Olloquequi, J., Castro-Torres, R. D., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-201106 · Cited by 25 · see citing works
Emerging phosphodiesterase inhibitors for treatment of neurodegenerative diseases
Xiang, Y., Naik, S. G., Zhao, L., Shi, J., & Ke, H. (2024) · Medicinal Research Reviews · doi:10.1002/med.22017 · Cited by 21 · see citing works
“Very recently, several studies at animal models 238,239 and at the preclinical stage (NCT02835716) showed that roflumilast potentiated improvement of cognitive impairment.”
BackgroundKeskin, H., Keskin, F., Tavacı, T., Halıcı, H., Yüksel, T. N., Özkaraca, M., Bilen, A., & Halıcı, Z. (2021) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13493 · Cited by 18 · see citing works
Mosalam, E. M., Atya, S. M., Mesbah, N. M., Allam, S., & Mehanna, E. T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073108 · Cited by 18 · see citing works
“It also acts by lowering the level of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α ), interferon-γ (IFN-γ ), nuclear factor kappa B (NF-κ B) and interleukin-17 (IL-17) [15].”
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
Ahmad, N., Lesa, K. N., Ujiantari, N. S. O., Sudarmanto, B. S. A., Fakhrudin, N., & Ikawati, Z. (2024) · Advances in Pharmacological and Pharmaceutical Sciences · doi:10.1155/2024/1230239 · Cited by 14 · see citing works
“In similar manner, second-generation PDE4 inhibitors, including rofumilast and cilomilast, augment memory and cognition, increase neurogenesis, and promote neuroplasticity of the hippocampus [18].”
BackgroundScope of adjuvant therapy using roflumilast, a PDE-4 inhibitor against COVID-19
Sugin Lal Jabaris, S., & Ranju, V. (2020) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2020.101978 · Cited by 14 · see citing works
Roy, D., Balasubramanian, S., Kunte, P. P., Natarajan, J., Sola, P., Rymbai, E., & Rajendra, P. K. M. (2024) · Journal of drug targeting · doi:10.1080/1061186x.2024.2408724 · Cited by 7 · see citing works
“…in various neurodegenerative and cNs diseases, such as aD, hD, sci as well as PD, its activity with nanoformulation remains unexplored in PD [23,32,56]. clinical data have shown that ROF displays a lower incidence of emesis and nausea compared to canonical PDe4 inhibitors such as rolipram [57].…”
Phosphodiesterase 4 (PDE4) and neurological disorders: A promising frontier in neuropharmacology
Nahid, S., Saeedi, S., & Hopkins, C. R. (2024) · Advances in pharmacology · doi:10.1016/bs.apha.2024.10.005 · Cited by 5 · see citing works
Gezer, A., & SARI, E. K. (2023) · PubMed Central · doi:10.22038/ijbms.2023.65948.14507 · Cited by 4 · see citing works
“Several new PDE4 inhibitor compounds are in early clinical development, and there is not yet clear information about their efficacy and safety (23).”
BackgroundRefaie, M. M. M., Ibrahim, M. F. G., Fawzy, M. A., Abdel‐Hakeem, E. A., Rahman, E. S. M. A. E., Zenhom, N. M., & Shehata, S. (2023) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2023.2222228 · Cited by 4 · see citing works
Taha, M., Salah, D. H. B., Abdou, K., & Senousy, M. A. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04682-1 · Cited by 3 · see citing works
Rectal roflumilast improves trinitrobenzenesulfonic acid-induced chronic colitis in rats
Shaikh-Omar, A., Murad, H. A., & Alotaibi, N. M. (2022) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x2021e11877 · Cited by 2 · see citing works
Tiwari, N., Kaur, A., Kaur, A., & Goel, R. K. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05429-9 · Cited by 2 · see citing works
“Roflumilast (ROF), a selective PDE4 inhibitor known for its ability to cross the blood–brain barrier (BBB), exhibits anti-inflammatory and immunomodulatory effects [29, 30].”
Kinch, C. D., Kesler, M., Dogra, D., Morin, K., Ibhazehiebo, K., Noschang, C. G., Rho, J. M., & Kurrasch, D. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.13.653835 · Cited by 1 · see citing works
Kaul, M., Sunkara, S., Major, M. J., Gordon, K. E., & Rubinstein, I. (2021) · Respirology · doi:10.1111/resp.14126
“Fifth, concurrent long-term treatment with oral roflumilast or an injectable IL-6 receptor antagonist is prescribed.(11,19,20) We propose that clinical trials comprising these five components be conducted in patients with severe COPD who express limited physical activity and exercise capacity to support or refute this…”
BackgroundTracking Neurodegeneration: Advancement in Experimental Study Models
Arumugam, M., & Sugin Lal Jabaris, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-6703-9_3
Identification of a novel PDE4 inhibitor inspired by leoligin-derived lignans
Coffey, C., Perhal, A. F., Richter, W., Chen, Y., Linder, T., Schwaiger, S., Mihovilovič, M. D., Kirchmair, J., Schnürch, M., & Dirsch, V. M. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118285
Sun, J., Shi, F., & Li, L. (2026) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2026.2615403
“…kinase (p38), and c-Jun N-terminal kinase ( JNK) activation, thereby suppressing the production of tNF-α and inflammation in macrophages, and it decreases the numbers of circulating leukocytes and eosinophils, which is associated with reducing the concentrations of il-4, il-5, and tNF-α [37].”
InfluentialNhung, N. T. H., Torazza, C., Leardi, R., Farinini, E., Schepers, M., Willems, E., Rosso, F., Bonanno, G., Vanmierlo, T., Fedele, E., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-11282050/v1
- Authors
- Sugin, L. J. S., Murugesan, A., Bindu, M., & Sunil, K. N.
- Affiliations
- Ministry of AYUSH (IN)
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 736
- Pages
- 135281
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W3045912918
- Cited by
- 24
- References
- 55
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 2
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- roflumilast, phosphodiesterase-4 inhibitors, cognitive impairment, Alzheimer's disease, age-associated memory impairment, cAMP signaling, CREB, brain-derived neurotrophic factor, hippocampus, memory
- MeSH terms
- Aminopyridines, Animals, Benzamides, Cyclopropanes, Humans, Memory, Phosphodiesterase 4 Inhibitors, Cognitive Dysfunction
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
