Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders Tangui Maurice To cite this version: Tangui Maurice. Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders. Expert Opinion on Drug Discovery, Informa Healthcare, 2020, 10.1080/17460441.2021.1838483. hal-03020731 HAL Id: hal-03020731 https://hal.archives-ouvertes.fr/hal-03020731 Submitted on 24 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders Tangui MAURICE MMDN, Univ Montpellier, EPHE, INSERM, UMR_S1198, Montpellier, France Correspondance: Dr T. Maurice, MMDN, INSERM UMR_S1198, Université de Montpellier, CC105, place EuGène Bataillon, 34095 Montpellier cedex 5, France. Tel.: +33/0 4 67 14 32 91. E-mail:
[email protected] Abstract Introduction: The sigma-1 receptor (S1R) is attracting much attention as a target for disease- modifying therapies in neurodegenerative diseases. It is a highly conserved protein, present in plasma and endoplasmic reticulum (ER) membranes and enriched in mitochondria-associated ER membranes (MAMs).