Low density of sigma1 receptors in early Alzheimer’s disease
Open accessAbstract
Objective The sigma(1) receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma(1) receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma(1) receptors in AD using [(11)C]SA4503 positron emission tomography (PET).Methods We studied five AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [(11)C]SA4503. A two-tissue three-compartment model was used to estimate K (1), k (2), k (3), k (4), and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k (3) to k (4) was computed as the binding potential (BP), which is linearly related to the density of sigma(1) receptors. Unpaired t tests were used to compare K (1) and BP in patients with AD and normal subjects.Results As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K (1) was significantly lower in the parietal lobe.Conclusions [(11)C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma(1) receptors is reduced in early AD.
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In very early phases of AD, a significant loss of σ1R occurs in the brain.
“Instead, in the very early phases of AD, a significant loss of σ1R occurs in the brain [115,116].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [115]
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“In fact, Sig-1R density is significantly lower in AD patients’ brains (68, 119, 167) and genetic studies demonstrated an association between SIGMAR1 polymorphisms and the risk for developing AD (42).”
Tsai, S., Pokrass, M. J., Klauer, N. R., Nohara, H., & Su, T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422001112 · Cited by 77 · see citing works
“Discussion Sig-1Rs have been reported to play a role in the pathogenesis of neurodegenerative disorders including AD (30, 45, 46), Parkinson’s disease (47, 48), and motor neuron disorders (49–51).”
BackgroundAssociation between a variant of the sigma-1 receptor gene and Alzheimer's disease
Fehér, Á., Juhász, A., László, A., Kalman, J. L., Pákáski, M., Kalman, J. L., & Janka, Z. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.04.046 · Cited by 75 · see citing works
Sigma-1 receptor chaperones in neurodegenerative and psychiatric disorders
Tsai, S., Pokrass, M. J., Klauer, N. R., Credico, N. E. D., & Su, T. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.972939 · Cited by 73 · see citing works
“Indeed, neuroimaging studies revealed that Sig-1Rs are present in lower density in brains from AD patients relative to the brains of healthy individuals [36].”
BackgroundTargeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders
Malar, D. S., Thitilertdecha, P., Ruckvongacheep, K. S., Brimson, S., Tencomnao, T., & Brimson, J. M. (2023) · CNS Drugs · doi:10.1007/s40263-023-01007-6 · Cited by 74 · see citing works
Moriguchi, S., Yamamoto, Y., Ikuno, T., & Fukunaga, K. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07256.x · Cited by 70 · see citing works
“PET study also revealed loss of sigma-1R from brain of AD patients (Mishina et al. 2008).”
BackgroundRijsketic, D. R., Wu, L., Wu, J., Kim, D. B., Rammes, G., Geva, M., Hayden, M. R., & Борисович, Б. И. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.12.022 · Cited by 69 · see citing works
“The density of S1R binding sites was reduced in several brain regions early in AD in PET imaging experiments with S1R radioligands (Mishina et al., 2008).”
BackgroundInfluentialFischer, S., Wiese, C., Maestrup, E. G., Hiller, A., Deuther‐Conrad, W., Scheunemann, M., Schepmann, D., Steinbach, J., Wünsch, B., & Brust, P. (2010) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-010-1658-z · Cited by 67 · see citing works
“Neuroimaging of σ1 receptors by PET in humans is currently being performed by the application of [(11)C]SA4503 which has been used in patients with Alzheimer’s and Parkinson’s disease [23, 24, 45].”
BackgroundMethodNaia, L., Ly, P., Mota, S., Lopes, C., Maranga, C., Coelho, P., Gershoni-Emek, N., Ankarcrona, M., Geva, M., Hayden, M., et al. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01022-9 · Cited by 67 · see citing works
“S1R was previously described in other neurodegenerative disorders in which oxidative stress is involved [48, 49], strengthening the potential protective effect of pridopidine by activating the S1R.”
BackgroundSubcellular Localization of the Sigma-1 Receptor in Retinal Neurons — an Electron Microscopy Study
Mavlyutov, T. A., Epstein, M. L., & Guo, L. (2015) · Scientific Reports · doi:10.1038/srep10689 · Cited by 65 · see citing works
The role of sigma-1 receptors in the pathophysiology of neuropsychiatric diseases
Hashimoto (2009) · Journal of Receptor Ligand and Channel Research · doi:10.2147/jrlcr.s8453 · Cited by 63 · see citing works
“• Decrease of sigma-1 receptors in the Alzheimer’s disease brain 85,86 Note: Summarized table of psychiatric diseases and relating substances and events regarding the sigma-1 receptor.”
Sigma-1 (σ1) Receptor in Memory and Neurodegenerative Diseases
Maurice, T., & Goguadze, N. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_15 · Cited by 62 · see citing works
Sigma-1 receptor: A potential target for the development of antidepressants
Wang, Y., Xia, C., Jia, H., He, J., Lian, W., Yan, Y., Wang, W., Zhang, W., & Xu, J. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2022.105390 · Cited by 57 · see citing works
Abate, C., Niso, M., Lacivita, E., Mosier, P. D., Toscano, A., & Perrone, R. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1013133 · Cited by 55 · see citing works
Balasuriya, D., D’Sa, L., Talker, R., Dupuis, E., Maurin, F., Martin, P., Borgèse, F., Soriani, O., & Edwardson, J. M. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.603506 · Cited by 54 · see citing works
Insights into the Sigma‐1 receptor Chaperone's cellular functions: A microarray report
Tsai, S., Rothman, R. K., & Su, T. (2011) · Synapse · doi:10.1002/syn.20984 · Cited by 52 · see citing works
“, 2005), as well as neurodegerative diseases, including Alzheimer’s disease, Parkinson’s disease, and motor neuron diseases (Luty et al., 2010; Mavlyutov et al., 2010; Meunier et al., 2006; Mishina et al., 2008).”
BackgroundInfluentialZhemkov, V., Geva, M., Hayden, M. R., & Борисович, Б. И. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084082 · Cited by 50 · see citing works
“Furthermore, S1R expression levels are reduced in sporadic ALS [20], Parkinson’s disease (PD), and Alzheimer’s disease (AD) patients [21,22].”
BackgroundMaestrup, E. G., Fischer, S., Wiese, C., Schepmann, D., Hiller, A., Deuther‐Conrad, W., Steinbach, J., Wünsch, B., & Brust, P. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900909e · Cited by 50 · see citing works
Behensky, A. A., Yasny, I. E., Shuster, A. M., Середенин, С. Б., Petrov, A. V., & Cuevas, J. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.208348 · Cited by 50 · see citing works
“It has been reported that there is a reduction in the number of s-ligand binding sites and s-1 receptors in the brains of patients with AD (Jansen et al., 1993, Mishina et al., 2008).”
BackgroundCellular stress responses in hepatitis C virus infection: Mastering a two-edged sword
Vasallo, C., & Gastaminza, P. (2015) · Virus Research · doi:10.1016/j.virusres.2015.03.013 · Cited by 47 · see citing works
Roles of sigma-1 receptors in Alzheimer's disease.
Jin, J., Fang, M., Zhao, Y., & Liu, X. (2015) · PubMed Central · Cited by 47 · see citing works
Sigma (σ) Receptors as Potential Therapeutic Targets to Mitigate Psychostimulant Effects
Matsumoto, R. R., Nguyen, L., Kaushal, N., & Robson, M. J. (2014) · Advances in pharmacology · doi:10.1016/b978-0-12-420118-7.00009-3 · Cited by 47 · see citing works
Maestrup, E. G., Wiese, C., Schepmann, D., Brust, P., & Wünsch, B. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.11.013 · Cited by 46 · see citing works
Using sigma-ligands as part of a multi-receptor approach to target diseases of the brain
Brimson, J. M., Brimson, S., Chomchoei, C., & Tencomnao, T. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1805435 · Cited by 46 · see citing works
Herrera‐Arozamena, C., Martí‐Marí, O., Estrada, M., Revenga, M. D. L. F., & Rodrı́guez-Franco, M. I. (2016) · Molecules · doi:10.3390/molecules21091165 · Cited by 42 · see citing works
“Moreover, a significant reduction in the overall levels of the σ1R protein has been recently reported in the AD-brains [102] and in the lumbar spinal cord of patients suffering amyotrophic lateral sclerosis (ALS) [103].”
BackgroundIs There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?
Colom, M., Vidal, B., & Zimmer, L. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00255 · Cited by 44 · see citing works
Sigma receptors and neurological disorders
Piechal, A., Jakimiuk, A. A., & Mirowska-Guzel, D. M. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00310-7 · Cited by 44 · see citing works
Role of σ1 Receptors in Learning and Memory and Alzheimer’s Disease-Type Dementia
Maurice, T., & Goguadze, N. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-50174-1_15 · Cited by 42 · see citing works
Pharmacokinetic and pharmacodynamic evaluation of donepezil for the treatment of Alzheimer's disease
Prvulovic, D., & Schneider, B. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.915028 · Cited by 41 · see citing works
“There is a substantial reduction of cortical sigma-1 receptor density by 44 -- 60% in Alzheimer’s disease [47] but not in physiological aging [48].”
BackgroundAfobazole Activation of σ-1 Receptors Modulates Neuronal Responses to Amyloid-β25–35
Behensky, A. A., Yasny, I. E., Shuster, A. M., Середенин, С. Б., Petrov, A. V., & Cuevas, J. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.208330 · Cited by 41 · see citing works
“A loss of s binding sites has been observed in AD, and specific s-1 receptor polymorphisms have been associated with altered risk for this disease (Jansen et al., 1993, Uchida et al., 2005, Mishina et al., 2008, Feher et al., 2012).”
BackgroundTargeting CaN/NFAT in Alzheimer’s brain degeneration
Mackiewicz, J., Lisek, M., & Boczek, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1281882 · Cited by 40 · see citing works
Pati, M. L., Hornick, J. R., Niso, M., Berardi, F., Spitzer, D., Abate, C., & Hawkins, W. G. (2017) · BMC Cancer · doi:10.1186/s12885-016-3040-4 · Cited by 39 · see citing works
Sun, Y., Yan, C., He, L., Xiang, S., Wang, P., Li, Z., Chen, Y., Zhao, J., Yuan, Y., Wang, W., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101899 · Cited by 40 · see citing works
PET Agents in Dementia: An Overview
van Waarde, A., Marcolini, S., Deyn, P. P. D., & Dierckx, R. (2021) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2020.12.008 · Cited by 38 · see citing works
Prasanth, M. I., Malar, D. S., Tencomnao, T., & Brimson, J. M. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.1939681 · Cited by 40 · see citing works
Loss of Sigma‐1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense
Weng, T.-Y., Hung, D. T., Su, T., & Tsai, S. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4582135 · Cited by 37 · see citing works
“Namely, mutations of the Sig-1R were found in amyotrophic lateral sclerosis (ALS) cohorts [24, 25], and reduced density of Sig-1Rs was observed in the cerebral and cerebellar regions of the brain in early Alzheimer’s disease (AD) patients [26].”
BackgroundYamoah, A., Tripathi, P., Sechi, A. S., Köhler, C. N., Guo, H., Chandrasekar, A., Nolte, K. W., Wruck, C. J., Katona, I., Anink, J. J., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-190722 · Cited by 35 · see citing works
“In addition, they have been shown to be abnormally modified in AD [74–77], Parkinson’s disease [75], Huntington’s disease [78], and ALS [33, 34, 67], disorders that feature distinct ultrastructural ER alterations and defective protein degradation pathways [79].”
Abate, C., Ferorelli, S., Contino, M., Marottoli, R., Colabufo, N. A., Perrone, R., & Berardi, F. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.05.057 · Cited by 36 · see citing works
He, Y., Xie, F., Ye, J., Deuther‐Conrad, W., Cui, B., Wang, L., Lu, J., Steinbach, J., Brust, P., Huang, Y. H., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01723 · Cited by 35 · see citing works
Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis
Couly, S., Khalil, B., Viguier, V., Roussel, J., Maurice, T., & Liévens, J.-C. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz267 · Cited by 33 · see citing works
“For instance, S1Rbinding sites are found decreased in the cerebral cortex and cerebellum of patients with schizophrenic illness (21, 22) or Alzheimer’s disease (23, 24).”
BackgroundAbate, C., Hornick, J. R., Spitzer, D., Hawkins, W. G., Niso, M., Perrone, R., & Berardi, F. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200591t · Cited by 35 · see citing works
Borbély, E., Varga, V. É., Szögi, T., Schuster, I., Bozsó, Z., Penke, B., & Fülöp, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052514 · Cited by 34 · see citing works
Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor
Maurice, T., Strehaïano, M., Duhr, F., & Chevallier, N. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.11.010 · Cited by 34 · see citing works
“cerebellum and thalamus in the brain of AD patients compared to controls [23].”
Hong, J., Wang, X., Zhang, T., Zhang, B., & Chen, L. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.08.007 · Cited by 33 · see citing works
Jia, H., Zhang, Y., & Huang, Y. H. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.07.033 · Cited by 32 · see citing works
Radiopharmaceuticals for positron emission tomography investigations of Alzheimer’s disease
Någren, K., Halldin, C., & Rinne, J. O. (2009) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-009-1301-z · Cited by 31 · see citing works
“Recently, a PET study using the sigma1 selective tracer [(11)C]SA4503 in five AD patients and seven healthy volunteers demonstrated that the density of cerebral and cerebellar sigma1 receptors were significantly reduced in the AD patients [114].”
Alamri, M. A. (2019) · Bioinformation · doi:10.6026/97320630015586 · Cited by 32 · see citing works
Dentoni, G., Castro‐Aldrete, L., Naia, L., & Ankarcrona, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.920228 · Cited by 31 · see citing works
“Positron emission tomography (PET) using a radioligand for the receptor was used confirming its depletion in the early stages of AD (Mishina et al., 2008).”
MethodIto, K., Hirooka, Y., & Sunagawa, K. (2013) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3182970b15 · Cited by 30 · see citing works
“The brain S1R is reported to decrease widely in regions, such as the cerebral cortex, cerebellum, and thalamus, in Alzheimer disease.(30) Therefore, the reduction of S1R may be caused ubiquitously in the brain of MI-mice, and it may be partly involved in sympathoexcitation and mental disorder.”
BackgroundRybczynska, A. A., Elsinga, P. H., Sijbesma, J. W. A., Ishiwata, K., de Jong, J. R., de Vries, E. F. J., Dierckx, R. A. J. O., & van Waarde, A. (2009) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-009-1076-2 · Cited by 30 · see citing works
“C-SA4503 has been used extensively for PET studies of animal tumours [2, 22–24] and the human brain [25–28].”
Method2‐Aminopyridine Derivatives as Potential σ2 Receptor Antagonists
Abate, C., Ferorelli, S., Niso, M., Lovicario, C., Infantino, V., Convertini, P., Perrone, R., & Berardi, F. (2012) · ChemMedChem · doi:10.1002/cmdc.201200246 · Cited by 30 · see citing works
Yin, J., Sha, S., Chen, T., Wang, C., Hong, J., Jie, P., Zhou, R., Li, L., Sokabe, M., & Chen, L. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.09.027 · Cited by 30 · see citing works
“emission tomography (PET) with [11C] SA4503 has revealed that the densities of cerebral and cerebellar s1R are reduced in early AD brains (Mishina et al., 2008).”
Brust, P., Deuther‐Conrad, W., Becker, G., Patt, M., Donat, C. K., Stittsworth, S., Fischer, S., Hiller, A., Wenzel, B., Dukić-Stefanović, S., et al. (2014) · Journal of Nuclear Medicine · doi:10.2967/jnumed.114.137562 · Cited by 29 · see citing works
“A reduction of 26% in postmortem 3H-1, 3 di-o-tolylguanidine (DTG) binding studies was detected in the hippocampus of Alzheimer’s patients (3), and in vivo 11C-SA4503 imaging studies demonstrated a reduction of at least 25% in the regions of interest in both Parkinson’s and Alzheimer’s patients (4,5).”
BackgroundMethodAbatematteo, F. S., Niso, M., Contino, M., Leopoldo, M., & Abate, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126359 · Cited by 29 · see citing works
“Importantly, in patients with AD, a reduction of σ1 receptor density [20] has been demonstrated.”
BackgroundThe Sigma Receptors in Alzheimer’s Disease: New Potential Targets for Diagnosis and Therapy
Wang, T., & Jia, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512025 · Cited by 29 · see citing works
The Sigma Enigma: A Narrative Review of Sigma Receptors
Pergolizzi, J. V., Varrassi, G., Coleman, M., Breve, F., Christo, D. K., Christo, P. J., & Moussa, C. (2023) · Cureus · doi:10.7759/cureus.35756 · Cited by 28 · see citing works
“It is believed that the loss of sigma-1 receptors in the brain occurs early in the course of Alzheimer’s disease, mainly affecting the frontal, temporal, and occipital lobes [67].”
BackgroundNiso, M., Riganti, C., Pati, M. L., Ghigo, D., Berardi, F., & Abate, C. (2015) · ChemBioChem · doi:10.1002/cbic.201402712 · Cited by 27 · see citing works
In vitro and in vivo sigma 1 receptor imaging studies in different disease states
Agha, H. M., & McCurdy, C. R. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00186d · Cited by 26 · see citing works
Wang, X., Li, D., Deuther‐Conrad, W., Lü, J., Xie, Y., Jia, B., Cui, M., Steinbach, J., Brust, P., Liu, B., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5009488 · Cited by 26 · see citing works
Li, Y., Wang, X., Zhang, J., Deuther‐Conrad, W., Xie, F., Zhang, X., Liu, J., Qiao, J., Cui, M., Steinbach, J., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301734g · Cited by 26 · see citing works
Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis.
Lisak, R., Nedelkoska, L., & Benjamins, J. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577188 · Cited by 22 · see citing works
Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection
Воронин, М. В., Абрамова, Е. В., Verbovaya, E. R., Vakhitova, Y. V., & Середенин, С. Б. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010823 · Cited by 27 · see citing works
“These results are consistent with positron emission tomography (PET) data, showing reduced distribution of cortical Sigma1R in the early phase of AD [162].”
ResultRole of Sigma-1 Receptor in Cocaine Abuse and Neurodegenerative Disease
Cai, Y. C., Yang, L., Niu, F., Liao, K., & Buch, S. J. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-50174-1_12 · Cited by 24 · see citing works
4-Nitro-2,1,3-benzoxadiazole derivatives as potential fluorescent sigma receptor probes
Schininà, B., Martorana, A., Colabufo, N. A., Contino, M., Niso, M., Perrone, M. G., Guidi, G. D., Catalfo, A., Rappazzo, G., Zuccarello, E., et al. (2015) · RSC Advances · doi:10.1039/c5ra08639f · Cited by 23 · see citing works
Mutational Analysis of Sigma-1 Receptor’s Role in Synaptic Stability
Ryskamp, D. A., Zhemkov, V., & Bezprozvanny, I. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01012 · Cited by 21 · see citing works
Maisonial‐Besset, A., Maestrup, E. G., Fischer, S., Hiller, A., Scheunemann, M., Wiese, C., Schepmann, D., Steinbach, J., Deuther‐Conrad, W., Wünsch, B., et al. (2011) · ChemMedChem · doi:10.1002/cmdc.201100108 · Cited by 21 · see citing works
Qian, B., Li, T., Zheng, Z.-X., Zhang, H., Xu, W., Mo, S.-M., Cui, J., Chen, W.-J., Lin, Y., & Lin, Z. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.134466 · Cited by 20 · see citing works
Maisonial‐Besset, A., Maestrup, E. G., Wiese, C., Hiller, A., Schepmann, D., Fischer, S., Deuther‐Conrad, W., Steinbach, J., Brust, P., & Wünsch, B. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.11.002 · Cited by 20 · see citing works
MERCs. The Novel Assistant to Neurotransmission?
Shirokova, O. M., Pchelin, P. V., & Mukhina, I. V. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.589319 · Cited by 20 · see citing works
“Besides, a life-time decline in SIGMA1R distribution was demonstrated in the cerebral cortex of patients with AD already at the early stage of the disease (Mishina et al., 2008).”
Background
- Authors
- Mishina, M., Ohyama, M., Ishii, K., Kitamura, S., Kimura, Y., Oda, K.-I., Kawamura, K., Sasaki, T., Kobayashi, S., Katayama, Y., & Ishiwata, K.
- Affiliations
- Tokyo Metropolitan Institute of Gerontology (JP)
- Nippon Medical School Musashi Kosugi Hospital (JP)
- Chiba Hokusou Hospital (JP)
- Nippon Medical School (JP)
- Corresponding author
- Mishina, Masahiro
- ORCID
- Venue
- Annals of Nuclear Medicine
- Published
- 2008-04
- Volume
- 22
- Issue
- 3
- Pages
- 151-156
- ISSN
- 0914-7187 (ISSN-L)
- 1864-6433
- OpenAlex
- W2169525045
- Cited by
- 172
- References
- 45
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 14 · 2019: 7 · 2018: 4 · 2017: 14 · 2016: 8 · 2015: 10 · 2014: 20 · 2013: 12 · 2012: 7
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- green
- repo.qst.go.jp
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Annals of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- QST-Repository (National Institutes for Quantum and Radiological Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- sigma-1 receptor, Alzheimer's disease, early Alzheimer's disease, receptor binding potential, receptor density
- MeSH terms
- Aged, Alzheimer Disease, Brain Chemistry, Carbon Radioisotopes, Cerebellum, Cerebral Cortex, Female, Humans, Male, Piperazines, Thalamus, Tissue Distribution, Receptors, sigma, Radiopharmaceuticals, Positron-Emission Tomography
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