{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:54:05Z","timestamp":1792220045509,"version":"4.4.0"},"reference-count":260,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7212203"],"award-info":[{"award-number":["7212203"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["22276016"],"award-info":[{"award-number":["22276016"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["21876013"],"award-info":[{"award-number":["21876013"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7212203"],"award-info":[{"award-number":["7212203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22276016"],"award-info":[{"award-number":["22276016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21876013"],"award-info":[{"award-number":["21876013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sigma (\u03c3) receptors are a class of unique proteins with two subtypes: the sigma-1 (\u03c31) receptor which is situated at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), and the sigma-2 (\u03c32) receptor, located in the ER-resident membrane. Increasing evidence indicates the involvement of both \u03c31 and \u03c32 receptors in the pathogenesis of Alzheimer\u2019s disease (AD), and thus these receptors represent two potentially effective biomarkers for emerging AD therapies. The availability of optimal radioligands for positron emission tomography (PET) neuroimaging of the \u03c31 and \u03c32 receptors in humans will provide tools to monitor AD progression and treatment outcomes. In this review, we first summarize the significance of both receptors in the pathophysiology of AD and highlight AD therapeutic strategies related to the \u03c31 and \u03c32 receptors. We then survey the potential PET radioligands, with an emphasis on the requirements of optimal radioligands for imaging the \u03c31 or \u03c32 receptors in humans. Finally, we discuss current challenges in the development of PET radioligands for the \u03c31 or \u03c32 receptors, and the opportunities for neuroimaging to elucidate the \u03c31 and \u03c32 receptors as novel biomarkers for early AD diagnosis, and for monitoring of disease progression and AD drug efficacy.<\/jats:p>","DOI":"10.3390\/ijms241512025","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:51:47Z","timestamp":1690509107000},"page":"12025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Sigma Receptors in Alzheimer\u2019s Disease: New Potential Targets for Diagnosis and Therapy"],"prefix":"10.3390","volume":"24","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China"},{"name":"Department of Nuclear Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref_1","unstructured":"Gauthier, S., Webster, C., Servaes, S., Morais, J.A., and Rosa-Neto, P. 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