Cited by 184Pharmacological Receptor Mechanisms and EffectsDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

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Low density of sigma1 receptors in early Alzheimer’s disease

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Mishina, Masahiro, Ohyama, Masashi, Ishii, Kenji, Kitamura, Shin, Kimura, Yuichi, Oda, Kei-ichi, Kawamura, Kazunori, Sasaki, Toru, Kobayashi, Shiro, Katayama, Yasuo, Ishiwata, Kiichi·2008·Annals of Nuclear Medicine

DOI 10.1007/s12149-007-0094-z

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Abstract

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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“Mini-mental state”
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056
Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease
Minoshima, S., Giordani, B., Berent, S., Frey, K. A., Foster, N. L., & Kuhl, D. E. (1997) · Annals of Neurology · doi:10.1002/ana.410420114 · Cited by 1,802
Untitled work
(1987) · PubMed · Cited by 1,147
Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET
Herholz, K., Salmon, E., Perani, D., Baron, J.-C., Holthoff, V., Frölich, L., Schönknecht, P., Ito, K., Mielke, R., & Kalbe, E. (2002) · NeuroImage · doi:10.1006/nimg.2002.1208 · Cited by 832
Sigma receptors: biology and function.
Walker, J. M., Bowen, W. D., Walker, F. O., Matsumoto, R. R., de Costa, B., & Rice, K. C. (1990) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)00047-x · Cited by 823
A proposal for the classification of sigma binding sites
Quirion, R., Bowen, W. D., Itzhak, Y., Junien, J., Musacchio, J. M., Rothman, R. B., Su, T., Tam, S. W., & Taylor, D. P. (1992) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(92)90030-a · Cited by 754
Steroid Binding at σ Receptors Suggests a Link Between Endocrine, Nervous, and Immune Systems
Su, T., London, E. D., & Jaffe, J. H. (1988) · Science · doi:10.1126/science.2832949 · Cited by 548
PET imaging of amyloid in Alzheimer's disease
Nordberg, A. K. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00853-1 · Cited by 462

Show all 45 references

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The pharmacology of sigma-1 receptors.
Maurice, T., & Su, T.-P. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.07.001 · Cited by 654
“It is worth mentioning that in a human positron emission tomography (PET) study employing [11C]SA4503, a lower density of sigma-1 receptors was found in early Alzheimer's patients compared to age-matched controls (Mishina et al., 2008).”
Result
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Hedskog, L., Pinho, C. M., Filadi, R., Rönnbäck, A., Hertwig, L., Wiehager, B., Larssen, P., Gellhaar, S., Sandebring, A., Westerlund, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300677110 · Cited by 478
“In concordance, decreased levels of σ1R have been detected postmortem in the hippocampus (37) and in living patients already at an early AD disease stage using imaging techniques (38).”
Background
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Izzo, N. J., Xu, J., Zeng, C., Kirk, M. J., Mozzoni, K., Silky, C., Rehak, C., Yurko, R., Look, G., Rishton, G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111899 · Cited by 157
“In severely demented Alzheimer’s disease patients (CDR stage 3) expected to have a high degree of cell loss, the density of sigma-2 receptors remains unchanged compared to age-matched normal individuals, while the density of the unrelated sigma-1 receptor is decreased by 54%, as has been previously reported [43].”
The sigma-1 receptor: roles in neuronal plasticity and disease
Kourrich, S., Su, T.-P., Fujimoto, M., & Bonci, A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.09.007 · Cited by 245
Role of sigma-1 receptors in neurodegenerative diseases
Nguyen, L., Lucke-Wold, B. P., Mookerjee, S. A., Cavendish, J. Z., Robson, M. J., Scandinaro, A. L., & Matsumoto, R. R. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.12.005 · Cited by 236
Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases
Ryskamp, D. A., Korban, S. A., Zhemkov, V., Kraskovskaya, N., & Борисович, Б. И. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00862 · Cited by 233
Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism
Francardo, V., Bez, F., Wieloch, T. W., Nissbrandt, H., Ruscher, K., & Cenci, M. A. (2014) · Brain · doi:10.1093/brain/awu107 · Cited by 209
“…neuroprotective effects of sigma-1 receptor (Sig-1R) ligands in animal models of brain disorders, including Alzheimer’s disease (Jansen et al., 1993; Mishina et al., 2008), amyotrophic lateral sclerosis (Mancuso et al., 2012; Prause et al., 2013), and stroke (Harukuni et al., 2000; Ajmo et al.,…”
Background
Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders
Hayashi, T., Tsai, S., Mori, T., Fujimoto, M., & Su, T. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.560837 · Cited by 209
“A binding assay using post-mortem brains and PET scans suggested the decrease of sigma-binding sites in brains with Alzheimer’s disease [86,120].”
Method
Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis
Prause, J. U., Goswami, A., Katona, I., Roos, A., Schnizler, M. K., Bushuven, E., Dreier, A., Buchkremer, S., Johann, S., Beyer, C., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt008 · Cited by 152
“Moreover, SigR1 has already been reported to be decreased in CNS tissue of early stage PD patients and in early AD (38,40,41).”
Background
The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease
Rijsketic, D. R., Wu, J., Geva, M., Kusko, R. L., Grossman, I., Hayden, M. R., & Борисович, Б. И. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.10.006 · Cited by 132
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“Sig-1R has so far been implicated in illnesses like AD [73, 74], PD [75], cancer [76], cardiac conditions [77] retinal dysfunction, perinatal and traumatic brain injury, ALS, HIV-related dementia, major depression, and psychostimulant addiction [78].”
Background
Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration
Öztürk, Z., O’Kane, C. J., & Pérez-Moreno, J. J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00048 · Cited by 136
Sigma receptors [σRs]: biology in normal and diseased states
Rousseaux, C. G., & Greene, S. F. (2015) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2015.1015737 · Cited by 123
“In fact, it has been suggested that the lack, or dysfunction, of s1R exacerbates ALS (774) and AD (42).”
Background
Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-κB pathway
Hyrskyluoto, A., Pulli, I., Törnqvist, K., Ho, T. H., Korhonen, L., & Lindholm, D. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.170 · Cited by 122
“14,21 Previously it was shown that the levels of Sig-1R are reduced in various neurodegenerative diseases such as AD and PD.15,16 The mechanisms involved and the functional significance of these changes, however, are not fully understood.”
Background
Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection
Nguyen, L., Lucke-Wold, B. P., Mookerjee, S. A., Kaushal, N., & Matsumoto, R. R. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-50174-1_10 · Cited by 119
“Mishina and colleagues, for example, used positron emission tomography (PET) with [11C] SA4530 to demonstrate reduced densities of sigma-1 receptors in the frontal, temporal and occipital lobes, cerebellum, and thalamus of early AD patients [138].”
The involvement of the sigma-1 receptor in neurodegeneration and neurorestoration
Ruscher, K., & Wieloch, T. W. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.11.011 · Cited by 110
The Oligomeric States of the Purified Sigma-1 Receptor Are Stabilized by Ligands
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“Because of the broad contributions of S1R in maintaining cellular homeostasis, the receptor has been identified as a therapeutic target for the treatment of cancer (34) and neurodegenerative diseases, including amyotrophic lateral sclerosis (35), Alzheimer (36), and Parkinson diseases (37), and for retinal neurodegene…”
Background
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van Waarde, A., Rybczynska, A. A., Ramakrishnan, N. K., Ishiwata, K., Elsinga, P. H., & Dierckx, R. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210793563365 · Cited by 103
“11 C-SA4503 has been successfully applied to PET studies of sigma-1 receptors in monkey [141, 142] and human [143-148] brain, including changes of receptor density in Alzheimer’s disease [149], Parkinson’s disease [150] or normal healthy ageing [142, 144], and assessment of sigma-1 receptor occupancy by CNS drugs [151…”
Background
Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s disease
Venkataraman, A. V., Mansur, A., Rizzo, G., Bishop, C., Lewis, Y., Kocagoncu, E., Lingford-Hughes, A., Huiban, M., Passchier, J., Rowe, J. B., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abk1051 · Cited by 101
Beyond symptomatic effects: potential of donepezil as a neuroprotective agent and disease modifier in Alzheimer's disease
Kim, S. H., Kandiah, N., Hsu, J., Suthisisang, C. C., Udommongkol, C., & Dash, A. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14030 · Cited by 100
“Aβ may also be involved in an inflammatory response in AD (Perini et al., 2002). σ1 receptors have been shown to be decreased in patients with AD (Mishina et al., 2008).”
Background
New Positron Emission Tomography (PET) Radioligand for Imaging σ-1 Receptors in Living Subjects
James, M. L., Shen, B., Zavaleta, C. L., Nielsen, C. H., Mésangeau, C., Vuppala, P. K., Chan, C. T., Avery, B. A., Fishback, J. A., Matsumoto, R. R., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300371c · Cited by 94
Sigma1 receptors inhibit store-operated Ca2+ entry by attenuating coupling of STIM1 to Orai1
Srivats, S., Balasuriya, D., Pasche, M., Vistal, G., Edwardson, J. M., Taylor, C. W., & Murrell‐Lagnado, R. D. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201506022 · Cited by 92
“Hyperactive SOCE may contribute to the motor deficiencies in σ1R-knockout mice (Maurice and Su, 2009; Sabino et al., 2009; Mavlyutov et al., 2010) and to neurodegeneration in Alzheimer’s (Mishina et al., 2008; Ishikawa and Hashimoto, 2009; Hyrskyluoto et al., 2013) and Parkinson’s diseases (Mishina et al., 2005; Hyrsk…”
Background
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies
Buccellato, F. R., D’Anca, M., Tartaglia, G. M., Del Fabbro, M., Scarpini, E., & Galimberti, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813900 · Cited by 94
“Instead, in the very early phases of AD, a signiﬁcant loss of σ 1R occurs in the brain [115,116].”
Background
Positron Emission Tomography Radiopharmaceuticals for Imaging Brain Beta-Amyloid
Vallabhajosula, S. (2011) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2011.02.005 · Cited by 95
The cholinergic system, sigma-1 receptors and cognition
van Waarde, A., Ramakrishnan, N. K., Rybczynska, A. A., Elsinga, P. H., Ishiwata, K., Nijholt, I. M., Luiten, P. G. M., & Dierckx, R. A. J. O. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.043 · Cited by 89
“%) in the frontal, temporal, and occipital lobe, cerebellum and thalamus of early AD patients as compared to healthy controls, but not in the hippocampus [109].”
Small Molecules Selectively Targeting Sigma-1 Receptor for the Treatment of Neurological Diseases
Ye, N., Qin, W., Tian, S., Xu, Q., Wold, E. A., Zhou, J., & Zhen, X.-C. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01192 · Cited by 89
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Mansur, A., Rabiner, E. A., Comley, R. A., Lewis, Y. L., Middleton, L. T., Huiban, M., Passchier, J., Tsukada, H., & Gunn, R. N. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.228080 · Cited by 85
AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer's Disease
Fisher, A., Борисович, Б. И., Wu, L., Ryskamp, D. A., Bar-Ner, N., Natan, N., Brandeis, R., Elkon, H., Nahum, V., Gershonov, E., et al. (2015) · Neurodegenerative Diseases · doi:10.1159/000440864 · Cited by 82
“Notably, decreased levels of σ1R have been detected in early stage AD patients [7], and that stimulation of σ1R alleviates the depressive symptoms, neuronal cell death and cognitive deficits in AD mouse models [8,9].”
Background
Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson’s Disease
Rodríguez‐Arribas, M., Yakhine-Diop, S. M. S., Pedro, J. M. B., Gómez‐Suaga, P., Gómez‐Sánchez, R., Martínez-Chacón, G., Fuentes, J. M., González‐Polo, R. A., & Niso‐Santano, M. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0140-8 · Cited by 82
“Although Sig-1R is important for UPR regulation during ER stress, it is shown to be decreased in several neurodegenerative disorders, including AD, HD, and PD [118, 119].”
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Resende, R., Fernandes, T., Pereira, A. C., Marques, A. P., & Pereira, C. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8231 · Cited by 78
“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).”
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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 79
“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).”
Background
Association 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 76
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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
“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].”
Background
Targeting 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 77
Sigma-1 receptor stimulation by dehydroepiandrosterone ameliorates cognitive impairment through activation of CaM kinase II, protein kinase C and extracellular signal-regulated kinase in olfactory bulbectomized mice
Moriguchi, S., Yamamoto, Y., Ikuno, T., & Fukunaga, K. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07256.x · Cited by 70
“PET study also revealed loss of sigma-1R from brain of AD patients (Mishina et al. 2008).”
Background
Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor
Rijsketic, 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 72
“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).”
BackgroundInfluential
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BackgroundMethod
The Sigma-1 Receptor Mediates Pridopidine Rescue of Mitochondrial Function in Huntington Disease Models
Naia, 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
“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.”
Background
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Mavlyutov, T. A., Epstein, M. L., & Guo, L. (2015) · Scientific Reports · doi:10.1038/srep10689 · Cited by 65
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“• 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 65
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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
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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
A Direct Interaction between the Sigma-1 Receptor and the hERG Voltage-gated K+ Channel Revealed by Atomic Force Microscopy and Homogeneous Time-resolved Fluorescence (HTRF®)
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 55
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“, 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).”
BackgroundInfluential
Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases
Zhemkov, V., Geva, M., Hayden, M. R., & Борисович, Б. И. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084082 · Cited by 50
“Furthermore, S1R expression levels are reduced in sporadic ALS [20], Parkinson’s disease (PD), and Alzheimer’s disease (AD) patients [21,22].”
Background
Evaluation of Spirocyclic 3-(3-Fluoropropyl)-2-benzofurans as σ1 Receptor Ligands for Neuroimaging with Positron Emission Tomography
Maestrup, 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
Stimulation of Sigma Receptors with Afobazole Blocks Activation of Microglia and Reduces Toxicity Caused by Amyloid-β25–35
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“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).”
Background
Cellular 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
Roles of sigma-1 receptors in Alzheimer's disease.
Jin, J., Fang, M., Zhao, Y., & Liu, X. (2015) · PubMed · Cited by 47
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
Synthesis, pharmacological activity and structure affinity relationships of spirocyclic σ1 receptor ligands with a (2-fluoroethyl) residue in 3-position
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
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
Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases
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
“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].”
Background
Is 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 47
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
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 43
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
“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].”
Background
Afobazole 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
“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).”
Background
Targeting 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 41
Sigma-2 receptor agonist derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer
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 40
Inhibition of ferroptosis through regulating neuronal calcium homeostasis: An emerging therapeutic target for Alzheimer’s disease
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
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 39
The emerging role of the sigma-1 receptor in autophagy: hand-in-hand targets for the treatment of Alzheimer’s
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
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 38
“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].”
Background
Aggregates of RNA Binding Proteins and ER Chaperones Linked to Exosomes in Granulovacuolar Degeneration of the Alzheimer’s Disease Brain
Yamoah, 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
“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].”
Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers
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
1-(4-[18F]Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine: A Novel Suitable Radioligand with Low Lipophilicity for Imaging σ1 Receptors in the Brain
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
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
“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).”
Background
Fluorescent Derivatives of σ Receptor Ligand 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a Tool for Uptake and Cellular Localization Studies in Pancreatic Tumor Cells
Abate, 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
Impact of Two Neuronal Sigma-1 Receptor Modulators, PRE084 and DMT, on Neurogenesis and Neuroinflammation in an Aβ1–42-Injected, Wild-Type Mouse Model of AD
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 35
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
“cerebellum and thalamus in the brain of AD patients compared to controls [23].”
Sigma-1 receptor knockout increases α-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra
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
Imaging sigma receptors in the brain: New opportunities for diagnosis of Alzheimer’s disease and therapeutic development
Jia, H., Zhang, Y., & Huang, Y. H. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.07.033 · Cited by 32
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 33
“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].”
Pharmacophore and docking-based sequential virtual screening for the identification of novel Sigma 1 receptor ligands
Alamri, M. A. (2019) · Bioinformation · doi:10.6026/97320630015586 · Cited by 32
The Potential of Small Molecules to Modulate the Mitochondria–Endoplasmic Reticulum Interplay in Alzheimer’s Disease
Dentoni, G., Castro‐Aldrete, L., Naia, L., & Ankarcrona, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.920228 · Cited by 32
“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).”
Method
Brain Sigma-1 Receptor Stimulation Improves Mental Disorder and Cardiac Function in Mice With Myocardial Infarction
Ito, K., Hirooka, Y., & Sunagawa, K. (2013) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3182970b15 · Cited by 30
“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.”
Background
Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats
Rybczynska, 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
“C-SA4503 has been used extensively for PET studies of animal tumours [2, 22–24] and the human brain [25–28].”
Method
2‐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
Sigma-1 (σ1) receptor deficiency reduces β-amyloid25–35-induced hippocampal neuronal cell death and cognitive deficits through suppressing phosphorylation of the NMDA receptor NR2B
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
“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).”
Distinctive In Vivo Kinetics of the New σ1 Receptor Ligands (R)-(+)- and (S)-(–)-18F-Fluspidine in Porcine Brain
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
“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).”
BackgroundMethod
Multi-Target Directed Ligands (MTDLs) Binding the σ1 Receptor as Promising Therapeutics: State of the Art and Perspectives
Abatematteo, F. S., Niso, M., Contino, M., Leopoldo, M., & Abate, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126359 · Cited by 31
“Importantly, in patients with AD, a reduction of σ1 receptor density [20] has been demonstrated.”
Background
The 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 30
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 29
“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].”
Background
Novel and Selective Fluorescent σ 2 ‐Receptor Ligand with a 3,4‐Dihydroisoquinolin‐1‐one Scaffold: A Tool to Study σ 2 Receptors in Living Cells
Niso, M., Riganti, C., Pati, M. L., Ghigo, D., Berardi, F., & Abate, C. (2015) · ChemBioChem · doi:10.1002/cbic.201402712 · Cited by 27
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
Novel Cyclopentadienyl Tricarbonyl 99m Tc Complexes Containing 1-Piperonylpiperazine Moiety: Potential Imaging Probes for Sigma-1 Receptors
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
Synthesis and Evaluation of Novel18F-Labeled Spirocyclic Piperidine Derivatives as σ1Receptor Ligands for Positron Emission Tomography Imaging
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
Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis
Lisak, R. P., Nedelkoska, L., & Benjamins, J. A. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577188 · Cited by 25
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
“These results are consistent with positron emission tomography (PET) data, showing reduced distribution of cortical Sigma1R in the early phase of AD [162].”
Result
Role 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
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
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
A 18F‐Labeled Fluorobutyl‐Substituted Spirocyclic Piperidine Derivative as a Selective Radioligand for PET Imaging of Sigma1 Receptors
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
The involvement of SigmaR1K142 degradation mediated by ERAD in neural senescence linked with CdCl2 exposure
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
Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoroalkyl homologs
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
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
“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: Mishina, Masahiro
Ishii, Kenji
Kitamura, Shin
Kimura, Yuichi
Kawamura, Kazunori
Sasaki, Toru
Ishiwata, Kiichi
Venue: Annals of Nuclear Medicine
Publisher: Springer Science and Business Media LLC
Published: 2008-04
Volume: 22
Issue: 3
Pages: 151-156
ISSN: 0914-7187 (ISSN-L)
1864-6433
DOI: 10.1007/s12149-007-0094-z
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 › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Low density of sigma1 receptors in early Alzheimer’s disease

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