USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and Aβ generation
Open accessAbstract
Down syndrome (DS), or trisomy 21, is one of the critical risk factors for early-onset Alzheimer's disease (AD), implicating key roles for chromosome 21-encoded genes in the pathogenesis of AD. We previously identified a role for the deubiquitinase USP25, encoded on chromosome 21, in regulating microglial homeostasis in the AD brain; however, whether USP25 affects amyloid pathology remains unknown. Here, by crossing 5×FAD AD and Dp16 DS mice, we observed that trisomy 21 exacerbated amyloid pathology in the 5×FAD brain. Moreover, bacterial artificial chromosome (BAC) transgene-mediated USP25 overexpression increased amyloid deposition in the 5×FAD mouse brain, whereas genetic deletion of Usp25 reduced amyloid deposition. Furthermore, our results demonstrate that USP25 promoted β cleavage of APP and Aβ generation by reducing the ubiquitination and lysosomal degradation of both APP and BACE1. Importantly, pharmacological inhibition of USP25 ameliorated amyloid pathology in the 5×FAD mouse brain. In summary, we identified the DS-related gene USP25 as a critical regulator of AD pathology, and our data suggest that USP25 serves as a potential pharmacological target for AD drug development.
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USP25, a ubiquitin-specific protease encoded on HSA21, is a critical regulator of AD pathology, promoting β cleavage of APP and Aβ generation by reducing ubiquitination and lysosomal degradation of APP and BACE1 in DS-AD mice.
“Furthermore, it was recently reported that USP25, a ubiquitin-specific protease encoded on HSA21, is a critical regulator of AD pathology, as it promotes β cleavage of APP and Aβ generation by reducing the ubiquitination and lysosomal degradation of both APP and BACE1 in DS-AD mice.19,20”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [19]
The Introduction identifies USP25 as chromosome 21–encoded, and the Results section on BACE1 deubiquitination and APP β cleavage shows that USP25 reduces APP and BACE1 ubiquitination and protects them from degradation. The Results on increased USP25 gene dosage also report greater amyloid pathology in a combined DS-AD mouse model. However, the cited mechanistic experiments were not shown in those DS-AD mice, so the claim’s final qualifier overstates where that mechanism was demonstrated. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrevious studies in mouse models of DS-AD have shown that independently of an extra copy of APP, other genes on HSA21 can increase Aβ plaque deposition at 5 and 6 months of age, indicating that genes act early in the pathological cascade.
“previous studies in mouse models of DS-AD have shown that independently of an extra copy of APP, other genes on HSA21 can increase Aβ plaque deposition at 5 and 6 months of age, indicating that genes act early in the pathological cascade.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [19]
The Results (page not provided) report increased Aβ plaques in 5-month-old 5×FAD;Dp16 mice and in 6-month-old mice overexpressing the chromosome 21 gene USP25. But the 5-month-old Dp16 mice also had increased APP, so that experiment does not establish an APP-copy-independent effect at 5 months. The Discussion reports a previous APP-copy-independent finding in another DS-AD mouse model, without specifying its age. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAn additional copy of HSA21 genes can alter APP biology, including Aβ deposition, in other APP transgenic models.
“Previous studies have indicated that an additional copy of HSA21 genes can alter APP biology, including Aβ deposition in other APP transgenic models.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [19]
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Cites
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569 · see citing works
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 1× · see citing works
“013530) and 5×FAD AD model mice (38) (stock no.”
BackgroundThe antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Self-citationEstrogen reduces neuronal generation of Alzheimer β-amyloid peptides
Xu, H., Gouras, G. K., Greenfield, J. P., Vincent, B., Näslund, J., Mazzarelli, L., Fried, G., Jovanovic, J. N., Seeger, M., Relkin, N. R., et al. (1998) · Nature Medicine · doi:10.1038/nm0498-447 · Cited by 557 · see citing works
Self-citationMueller-Steiner, S., Zhou, Y.-G., Arai, H., Roberson, E., Sun, B.-G., Chen, J., Wang, X., Yu, G.-Q., Esposito, L., Mucke, L., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.027 · Cited by 466 · see citing works
Self-citationInhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes
Ly, P. T. T., Wu, Y., Zou, H., Wang, R., Zhou, W., Kinoshita, A., Zhang, M., Yang, Y., Cai, F., Woodgett, J., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64516 · Cited by 442 · see citing works
Self-citationO’Connor, T., Sadleir, K. R., Maus, E., Velliquette, R. A., Zhao, J., Cole, S. L., Eimer, W. A., Hitt, B. D., Bembinster, L. A., Lammich, S., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.047 · Cited by 422 · see citing works
Alzheimer's disease in Down's syndrome: Clinicopathologic studies
Wisniewski, K. E., Dalton, A. J., McLachlan, D. R. C., Wen, G. Y., & Wisniewski, H. M. (1985) · Neurology · doi:10.1212/wnl.35.7.957 · Cited by 417 · 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
Self-citationDysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases
Zheng, Q., Huang, T. Y., Zhang, L., Zhou, Y., Luo, H., Xu, H., & Wang, X. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00303 · Cited by 312 · see citing works
Self-citationRyoo, S., Cho, H., Lee, H. W., Jeong, H. K., Radnaabazar, C., Kim, Y., Kim, M., Son, M., Seo, H., Chung, S., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05075.x · Cited by 227 · see citing works
Self-citationLi, Z., Yu, T., Morishima, M., Pao, A., LaDuca, J., Conroy, J., Nowak, N., Matsui, S.-I., Shiraishi, I., & Yu, Y. E. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm086 · Cited by 218 · see citing works
Leverenz, J. B., & Raskind, M. A. (1998) · Experimental Neurology · doi:10.1006/exnr.1997.6777 · Cited by 214 · see citing works
Zhong, B., Liu, X., Wang, X., Chang, S. H., Liu, X., Wang, A., Reynolds, J. M., & Dong, C. (2012) · Nature Immunology · doi:10.1038/ni.2427 · Cited by 206 · see citing works
Self-citationA prospective 14‐year longitudinal follow‐up of dementia in persons with D own syndrome
McCarron, M., McCallion, P., Reilly, E., & Mulryan, N. (2013) · Journal of Intellectual Disability Research · doi:10.1111/jir.12074 · Cited by 194 · see citing works
Lane, R. F., Raines, S. M., Steele, J., Ehrlich, M. E., Lah, J. J., Small, S. A., Tanzi, R. E., Attie, A., & Gandy, S. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3872-10.2010 · Cited by 165 · see citing works
Positive and negative regulation of APP amyloidogenesis by sumoylation
Li, Y., Wang, H., Wang, S., Quon, D. H., Liu, Y.-W., & Cordell, B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0235361100 · Cited by 165 · see citing works
Sun, X., He, G., & Song, W. (2006) · The FASEB Journal · doi:10.1096/fj.05-5632com · Cited by 156 · see citing works
Self-citationWiseman, F. K., Pulford, L. J., Barkus, C., Liao, F., Portelius, E., Webb, R., Chávez-Gutiérrez, L., Cleverley, K., Noy, S., Sheppard, O., et al. (2018) · Brain · doi:10.1093/brain/awy159 · Cited by 133 · see citing works
BACE1 Cleavage Site Selection Critical for Amyloidogenesis and Alzheimer's Pathogenesis
Zhang, S., Wang, Z., Cai, F., Zhang, M., Wu, Y., Zhang, J., & Song, W. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0340-17.2017 · Cited by 131 · see citing works
Self-citationYu, T., Liu, C., Belichenko, P., Clapcote, S. J., Li, S., Pao, A., Kleschevnikov, A., Bechard, A. R., Asrar, S., Chen, R., et al. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.107 · Cited by 127 · see citing works
Deubiquitinating enzymes (DUBs): decipher underlying basis of neurodegenerative diseases
Liu, B., Ruan, J., Chen, M., Li, Z., Manjengwa, G. M., Schlüter, D., Song, W., & Wang, X. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01233-8 · Cited by 103 · see citing works
Self-citationAyadi, A. E., Stieren, E. S., Barral, J. M., & Boehning, D. F. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206786109 · Cited by 93 · see citing works
Wrigley, J. D. J., Gavory, G., Simpson, I. D., Preston, M., Plant, H., Bradley, J., Goeppert, A. U., Rozycka, E., Davies, G. M., Walsh, J. J., et al. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00334 · Cited by 87 · see citing works
Del Prete, D., Rice, R. C., Rajadhyaksha, A. M., & D'Adamio, L. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.733626 · Cited by 86 · see citing works
Zheng, Q., Li, G., Wang, S., Zhou, Y., Liu, K., Gao, Y., Zhou, Y., Zheng, L., Zhu, L., Deng, Q., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe1340 · Cited by 85 · see citing works
Self-citationIslet amyloid polypeptide: Another key molecule in Alzheimer’s pathogenesis?
Zhang, Y., & Song, W. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.03.001 · Cited by 78 · see citing works
Self-citationBACE2, a conditional β-secretase, contributes to Alzheimer’s disease pathogenesis
Wang, Z., Xu, Q., Cai, F., Liu, X., Wu, Y., & Song, W. (2019) · JCI Insight · doi:10.1172/jci.insight.123431 · Cited by 78 · see citing works
Self-citationWatanabe, T., Hikichi, Y., Willuweit, A., Shintani, Y., & Horiguchi, T. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5659-11.2012 · Cited by 75 · see citing works
Yeates, E. F. A., & Tesco, G. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.718023 · Cited by 74 · see citing works
Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease in Down syndrome
Sun, X., Tong, Y., Qing, H., Chen, C.-H., & Song, W. (2006) · The FASEB Journal · doi:10.1096/fj.05-5628com · Cited by 63 · see citing works
Self-citationDifferential Oligomerization of the Deubiquitinases USP25 and USP28 Regulates Their Activities
Sauer, F., Klemm, T., Kollampally, R. B., Teßmer, I., Nair, R. K., Popov, N., & Kisker, C. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.02.029 · Cited by 61 · see citing works
Kang, E. L., Biscaro, B., Piazza, F., & Tesco, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407072 · Cited by 55 · see citing works
Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome
Mok, K. Y., Jones, E. L., Hanney, M., Harold, D., Sims, R., Williams, J., Ballard, C., & Hardy, J. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.022 · Cited by 48 · see citing works
Wolvetang, E. J., Bradfield, O., Tymms, M. J., Zavarsek, S., Hatzistavrou, T., Kola, I., & Hertzog, P. J. (2003) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(03)00121-0 · Cited by 42 · see citing works
Wu, Y., Ly, P. T. T., & Song, W. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8704-y · Cited by 41 · see citing works
Self-citationBelbin, O., Xiao, M.-F., Xu, D., Carmona-Iragui, M., Pegueroles, J., Benejam, B., Videla, L., Fernández, S., Barroeta, I., Nuñez-Llaves, R., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00398-0 · Cited by 39 · see citing works
miR155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer's disease
Readhead, B., Haure-Mirande, J.-V., Mastroeni, D., Audrain, M., Fanutza, T., Kim, S. H., Blitzer, R. D., Gandy, S., Dudley, J. T., & Ehrlich, M. E. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02185-z · Cited by 37 · see citing works
Williamson, R., Laulagnier, K., Miranda, A. M., Fernandez, M. A., Wolfe, M. S., Sadoul, R., & Paolo, G. D. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.818138 · Cited by 28 · see citing works
Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue
Lemoine, L., Ledreux, A., Mufson, E. J., Perez, S. E., Šimić, G., Doran, E. W., Lott, I. T., Carroll, S. L., Bharani, K., Thomas, S., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00414-3 · Cited by 26 · see citing works
Mechanistic Analysis of Age-Related Clinical Manifestations in Down Syndrome
Chen, X., Xing, Z., Chen, Q.-D., Salvi, R., Zhang, X., Tycko, B., Mobley, W. C., & Yu, Y. E. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.700280 · Cited by 22 · see citing works
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Sorted by citations
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Self-citationUSP25 Ameliorates Pathological Cardiac Hypertrophy by Stabilizing SERCA2a in Cardiomyocytes
Ye, B., Zhou, H., Chen, Y., Luo, W., Lin, W., Zhao, Y., Han, J., Han, X., Huang, W., Wu, G., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.321849 · Cited by 143 · see citing works
Self-citationPeripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis
Zhang, S., Gao, Y., Zhao, Y., Huang, T. Y., Zheng, Q., & Wang, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00812-5 · Cited by 78 · see citing works
Self-citationAli, M., Timsina, J., Western, D., Liu, M., Beric, A., Budde, J., Do, A., Heo, G., Wang, L., Gentsch, J., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.02.014 · Cited by 61 · see citing works
She, L., Li, X., Li, L., Zhang, J., Sun, J., Wu, H., Ren, J., Wang, W., Zhao, X., & Liang, G. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114192 · Cited by 45 · see citing works
USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2
Li, Z., Liu, B., Lambertsen, K. L., Clausen, B. H., Zhu, Z., Du, X., Xu, Y., Poulsen, F. R., Halle, B., Bonde, C., et al. (2023) · Advanced Science · doi:10.1002/advs.202301641 · Cited by 35 · see citing works
Self-citationWang, M.-D., Zhang, S., Liu, X., Wang, P., Zhu, Y.-F., Zhu, J., Lv, C.-S., Li, S., Liu, S.-F., & Wen, L. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01125-3 · Cited by 33 · see citing works
DUBs in Alzheimer’s disease: mechanisms and therapeutic implications
Qin, B., Chen, X., Wang, F., & Wang, Y. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02237-3 · Cited by 33 · see citing works
USP25 ameliorates diabetic nephropathy by inhibiting TRAF6-mediated inflammatory responses
Liu, B., Miao, X., Shen, J., Lou, L., Chen, K., Mei, F., Chen, M., Su, X., Du, X., Zhu, Z., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110877 · Cited by 28 · see citing works
Self-citationSun, J., Chen, F., She, L., Zeng, Y., Tang, H., Ye, B., Zheng, W., Xiong, L., Li, L., Li, L., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.11.020 · Cited by 24 · see citing works
Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches
Farrell, C., Mumford, P., & Wiseman, F. K. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.909669 · Cited by 22 · see citing works
Zhang, N., Nao, J., & Dong, X. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c06672 · Cited by 22 · see citing works
Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer’s Disease
Jia, F., & Fu, L. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04739-2 · Cited by 21 · see citing works
Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer’s Disease Treatment
Song, Y., Zhu, X., Zhang, X.-M., & Xiong, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179703 · Cited by 21 · see citing works
Self-citationHeterozygous variants in USP25 cause genetic generalized epilepsy
Fan, C.-X., Liu, X., Mei, D., Li, B.-M., Li, W., Xie, H., Wang, J., Shen, N.-X., Ye, Z.-L., You, Q.-L., et al. (2024) · Brain · doi:10.1093/brain/awae191 · Cited by 20 · see citing works
Ye, B., Xu, D., Zhong, L., Wang, Y., Wang, W., Xu, H., Han, X., Min, J., Wu, G., Huang, W., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70243 · Cited by 19 · see citing works
Self-citationEnhanced Gasdermin-E-mediated Pyroptosis in Alzheimer’s Disease
Wang, Q., Guo, S., Hu, D., Dong, X., Meng, Z., Jiang, Y., Feng, Z., Zhou, W., & Song, W. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.11.004 · Cited by 18 · see citing works
Self-citationZhang, Q., Xing, M., Bao, Z., Xu, L., Bai, Y., Chen, W., Pan, W., Cai, F., Wang, Q., Guo, S., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01768-6 · Cited by 18 · see citing works
Self-citationZhou, L., Qin, B., Yassine, D. M., Luo, M., Liu, X., Wang, F., & Wang, Y. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115624 · Cited by 17 · see citing works
Wu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F., Verdoes, M., Fisher, E. M. C., & Wiseman, F. K. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01632-8 · Cited by 16 · see citing works
Self-citationGuo, Y., Cai, C., Zhang, B., Tan, B., Tang, Q., Lei, Z., Qi, X., Chen, J., Zheng, X., Zi, D., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00146-7 · Cited by 16 · see citing works
USP25 contributes to defective neurogenesis and cognitive impairments
Cai, F., Song, B., Yang, Y., Liao, H., Li, R., Wang, Z., Cao, R., Chen, H., Wang, J., Wu, Y., et al. (2023) · The FASEB Journal · doi:10.1096/fj.202300057r · Cited by 12 · see citing works
Self-citationSaponin components in Polygala tenuifolia as potential candidate drugs for treating dementia
Li, S., Hou, Z., Ye, T., Song, X., Hu, X., & Chen, J. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1431894 · Cited by 15 · see citing works
Liu, Z., Liu, J., Wei, Y.-P., Li, J.-T., Zhang, J.-X., Yu, R., Yang, Q., Miao, Y.-L., & Dong, W.-G. (2025) · Cell Death and Disease · doi:10.1038/s41419-024-07315-z · Cited by 13 · see citing works
Aging and perioperative brain health: Mechanisms, management, and future
Cong, P., Chen, Q., Wu, Q., Wang, J., Huang, X., Zhang, Q., Chen, Z., Wu, H., Zhang, Y., He, M., et al. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003735 · Cited by 11 · see citing works
Self-citationMeningeal lymphatics as a therapeutic target for neurodegenerative disorders
Feng, Y., Wang, S., Xia, H., Jiang, X., Wu, M., Pan, S., & Song, W. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00528-y · Cited by 11 · see citing works
Self-citationGenetic architecture of hippocampus subfields volumes in Alzheimer’s disease
Cai, J., Xiong, W., Wang, X., Tan, H., & Database, T. A. D. N. I. (. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14110 · Cited by 9 · see citing works
Self-citationPCP4 Promotes Alzheimer’s Disease Pathogenesis by Affecting Amyloid-β Protein Precursor Processing
Hu, D., Dong, X., Wang, Q., Liu, M., Luo, S., Meng, Z., Feng, Z., Zhou, W., & Song, W. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230192 · Cited by 10 · see citing works
Self-citationZhao, M., Jin, Y., Yan, Z., He, C., You, W., Zhu, Z., Wang, R., Chen, Y., Luo, J., Zhang, Y., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217270 · Cited by 9 · see citing works
Self-citationLiu, X., Chen, P., Wu, W., Zhong, M., Dong, S., Lin, H., Dai, C., Zhang, Z., Lin, S., Che, C., et al. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123085 · Cited by 9 · see citing works
Lazzarino, G., Amorini, A. M., Mangione, R., Saab, M. W., Stasio, E. D., Rosa, M. D., Tavazzi, B., Lazzarino, G., Onder, G., & Carfì, A. (2022) · Antioxidants · doi:10.3390/antiox11061208 · Cited by 9 · see citing works
Zhang, Q., Liu, J., Liu, H., Ao, L., Yang, X., & Chen, D. (2024) · Scientific Reports · doi:10.1038/s41598-024-54541-8 · Cited by 9 · see citing works
Self-citationJia, S., Li, Q., Rui, X., Qin, W., Zhang, W., Dou, J., & Zhang, X. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1730206 · Cited by 8 · see citing works
Self-citationAraya, P., Niemeyer, B., Schade, K., Dunn, L. N., Waugh, K., Busquet, N., Brindley, C., Brown, C., Winkler, C., Lyford, H. R., et al. (2025) · iScience · doi:10.1016/j.isci.2025.113130 · Cited by 7 · see citing works
“19,20 26–29 Notably, both individuals with DS and mouse models of DS experience constitutive hyperactivation of interferon (IFN) signaling with signs of chronic inflammation and immune dysregulation, 30–40 that could exacerbate the neuroinflammatory response.”
Luo, R., Kang, Y., Ma, H., Zhang, Z., Hölscher, C., Li, H., & Zhang, Z. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114612 · Cited by 7 · see citing works
Regulation of USP25 by SP1 Associates with Amyloidogenesis
Li, R., Song, B., Xu, L., Zheng, J., Pan, W., Cai, F., Wang, J., Wu, Y., & Song, W. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221184 · Cited by 7 · see citing works
Self-citationZhang, Y., Guan, W., & Miao, Y. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117085 · Cited by 6 · see citing works
Self-citationMyeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease
Cui, Y., Zhang, X., Liu, J., Hou, Y., Qiao, S., Cao, M., Zhang, J., Wang, X., Liu, C., Wang, P., et al. (2024) · Aging Cell · doi:10.1111/acel.14260 · Cited by 6 · see citing works
Self-citationCheng, R., Bai, N., Liu, S., Zhao, X., Jiang, B., Guo, W., Cao, S., Liu, J., Li, N., Li, X., et al. (2024) · Science Signaling · doi:10.1126/scisignal.ado1035 · Cited by 6 · see citing works
Sterling, K., Cao, R., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01321-x · Cited by 6 · see citing works
Self-citationEffects of USP25 knockout on the gut microbial diversity and composition in mice
Li, J., Chen, Z., Yan, X., Chen, Q., Chen, C., Liu, H., & Shen, J. (2025) · BMC Microbiology · doi:10.1186/s12866-025-04035-y · Cited by 5 · see citing works
Wang, Q., 重庆医科大学附属儿童医院, 国., Jiang, Y., Meng, Z., Dong, X., Hu, D., Ji, L., Zhou, W., Song, W., 温州医科大学老年研究所第二附属医院, 育., et al. (2024) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2023.363 · Cited by 4 · see citing works
Self-citationTim-3 promotes viral infection by suppressing the USP25-TRAF3-IRF7 signaling pathway
Du, L., Chen, J., Du, C., Chen, J., Wang, Z., Bao, B., Zhonglin, L. V., Chen, X., Liang, M., Wang, L., et al. (2025) · Cellular Immunology · doi:10.1016/j.cellimm.2025.104930 · Cited by 4 · see citing works
Self-citationJia, X., Jiang, S., Cheng, H., Wang, Z., Chen, Z., Dong, W., Zhong, H., Zhang, Q., Song, X., Zhang, S., et al. (2025) · Blood · doi:10.1182/blood.2023023352 · Cited by 4 · see citing works
Self-citationSantelices, J., Schultz, A. C., Walker, A., Adams, N., Tirado, D., Barker, H. A., Eshraghi, A., Czyż, D. M., & Ferraro, M. J. (2025) · mBio · doi:10.1128/mbio.00312-25 · Cited by 4 · see citing works
Munavar-K, F., & Lenka, N. (2025) · Tissue Barriers · doi:10.1080/21688370.2025.2504738 · Cited by 5 · see citing works
USP10 in Neurological Disorders: Mechanistic Insights and Emerging Therapeutic Strategies
Celemuge, Sun, H., Zhang, J., Yang, Y., Mao, J., & Cheliger (2025) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.70144 · Cited by 3 · see citing works
Cui, J., Huang, R., & Dong, X. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.178706 · Cited by 3 · see citing works
USP25 regulates atherosclerosis by restricting RIPK1-mediated inflammatory responses
Su, X., Zhou, B., Xu, Y., Du, X., Chen, J., Yin, M., Miao, X., Zhao, Y., Wang, D., Zhu, Z., et al. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106213 · Cited by 3 · see citing works
Self-citationStructure Merging Approach Leads to New Dual Potent and Selective USP25/USP28 Inhibitors
Hernández‐Olmos, V., Patzke, J. V., Stone, C. E., Nair, R. K., Weller, K., Sauer, F., Endres, E., Jamai, O., Rachor, L., Warmutz, C. H., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03045 · Cited by 3 · see citing works
Xu, R., Huang, F., Liu, Q., Lv, Y., Hu, L., & Zhang, Q. (2024) · Renal Failure · doi:10.1080/0886022x.2024.2338932 · Cited by 3 · see citing works
Self-citationUSP25 inhibition ameliorates Parkinson’s disease by restoring mitophagy
Xu, Y., Jin, K., Chen, J., Li, Z., Zhu, Z., Su, X. W., Shen, J., Zhou, B., Cao, Z., Lou, L., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2516471123 · Cited by 2 · see citing works
Self-citationUbiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress
Yan, Y., Wang, X., Jeon, H., Kee, T. R., Tran, K. D., Lee, H., Zhao, X., Liu, T., Wing, S. S., Woo, J. A., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2514355123 · Cited by 2 · see citing works
Self-citationRoles of deubiquitinases in urologic cancers (Review)
Wu, L., Wang, J., Chai, L., Chen, J., & Jin, X. (2024) · Oncology Letters · doi:10.3892/ol.2024.14743 · Cited by 2 · see citing works
Wu, Y., Cleverley, K., & Wiseman, F. K. (2025) · PLoS ONE · doi:10.1371/journal.pone.0316822 · Cited by 1 · see citing works
Self-citationUse of anti–amyloid‐β monoclonal antibodies in persons with Down syndrome Alzheimer's disease
Farrell, C., Saini, F., Beidas, M. M., Ryan, N. S., Strydom, A., & Wiseman, F. K. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71404 · Cited by 1 · see citing works
Li, X., Xing, Z., Fang, H., Zhao, M., Li, Q., Feng, N., & Xu, F. (2026) · Scientific Reports · doi:10.1038/s41598-026-49272-x · Cited by 1 · see citing works
Wu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F. J., Verdoes, M., Fisher, E., & Wiseman, F. K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.20.545700 · Cited by 1 · see citing works
Self-citationSamy, M. V. G., & Perumal, S. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01348-0
Jandy, M., Hu, H., Liu, Y., & Bhattacharyya, A. (2025) · Springer eBooks · doi:10.1007/978-3-031-78611-2_7
Cocktail gene therapy (CGT) for neurodegenerative diseases: Targeting protein clearance systems
Zhang, H., & Teplow, D. B. (2025) · Medical Hypotheses · doi:10.1016/j.mehy.2025.111814
Self-citationWu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F., Verdoes, M., Fisher, E., & Wiseman, F. K. (2023) · Figshare · doi:10.6084/m9.figshare.23949660
Self-citationXie, B., Li, J., Huang, G., Zhao, Y., Chen, D., Wei, L., Guo, F., Florentino, R. M., Faccioli, L. A. P., Kurihara, T., et al. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.101002
Self-citationYang, Y., Jia, L., Xu, J., Wu, J., Huang, H., Yang, H., Qi, Z., Wang, Y., Yu, H., & Wang, S. (2026) · Cell Death Discovery · doi:10.1038/s41420-026-03159-y
Calcium Overloading-Induced UBE2O Upregulation Alleviates Neuronal Apoptosis
Jin, J., Yang, Z., Kang, A., Zhao, Y., Cai, Z., Qiu, M., Song, W., & Wu, Y. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06034-0
Self-citationUbiquitin-specific protease 25: a new regulator for cardiovascular and cerebrovascular diseases
Shao, Y., Jiang, S., Zhai, L., & Sun, F. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1802539
Deubiquitinase inhibitors: from evolving concepts to preclinical evaluation
Maubach, G., Hamann, L., Stein, M., Haak, E., & Naumann, M. (2026) · Drug Discovery Today · doi:10.1016/j.drudis.2026.104751
Joshi, A., Salunkhe, J., & Ugale, V. G. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12722-w
New mouse models for Down syndrome Alzheimer's disease
Wiseman, F. K. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261488873
Presenilin 1 Mutations Converge on Aβ42/Aβ40 Elevation via Distinct Mechanisms
Bestard‐Lorigados, I., Sterling, K., Li, L., Lin, Z., Wu, Z., Zhu, Q., Pan, W., Cai, F., & Song, W. (2026) · MedComm · doi:10.1002/mco2.70978
Self-citationEnzyme−Targeted Therapeutics for Neurological Disorders
Massignan, L., Lokesh, K., Ziadat, S., Uehling, D., Weaver, D. F., & Reed, M. A. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01274
Shi, X., Chen, G., Wang, X., Ma, R., & Li, G. (2026) · Biomolecules · doi:10.3390/biom16101494
Self-citationMicroglia in Alzheimer’s disease: from pathogenic mechanisms to therapeutic targeting
Tang, L., Li, X., Ran, Z., Qin, Z.-Z., Chen, S., Zhang, M., Zhou, L., Wang, W., & Chen, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1952810
A Novel Peptide Targeting the USP25 – SIRT1 Interaction Activates SIRT1 to Suppress Cell Senescence
Zhou, Y., Wang, X., Zhang, J., Qiang, H., Zhao, X., Luo, J., Ji, Y., Yao, J., Zhai, L., Zhang, T., et al. (2026) · Aging Cell · doi:10.1111/acel.70786
Self-citation
- Authors
- Zheng, Q., Song, B., Li, G., Cai, F., Wu, M., Zhao, Y., Jiang, L., Guo, T., Shen, M., Hou, H., Zhou, Y., Zhao, Y., Di, A., Zhang, L., Zeng, F., Zhang, X.-F., Luo, H., Zhang, X., Zhang, H., Zeng, Z., Huang, T. Y., Dong, C., Qing, H., Zhang, Y., Zhang, Q., Wang, X., Wu, Y., Xu, H., Song, W., & Wang, X.
- Affiliations
- Xiamen University (CN)
- University of British Columbia (CA)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Tsinghua University (CN)
- Beijing Institute of Technology (CN)
- Wenzhou Medical University (CN)
- Corresponding author
- Song, Weihong
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2022-03-01
- Volume
- 132
- Issue
- 5
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC8884900
- OpenAlex
- W4214883623
- Cited by
- 73
- References
- 42
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 15 · 2023: 16 · 2022: 4
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Investigation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- CIHR (PJT-166127)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- USP25, Alzheimer's disease, Down syndrome, amyloid-beta, APP processing, BACE1, ubiquitination, lysosomal degradation, microglia, 5xFAD mice, deubiquitinase, therapeutic target
- MeSH terms
- Alzheimer Disease, Amyloidosis, Animals, Brain, Disease Models, Animal, Down Syndrome, Flavin-Adenine Dinucleotide, Mice, Transgenic, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Ubiquitin Thiolesterase, Mice, Amyloid Precursor Protein Secretases
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