Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders

The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in...

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Bibliographic Details
Published in:CNS drugs 2023-05, Vol.37 (5), p.399-440
Main Authors: Malar, Dicson S., Thitilertdecha, Premrutai, Ruckvongacheep, Kanokphorn S., Brimson, Sirikalaya, Tencomnao, Tewin, Brimson, James M.
Format: Article
Language:English
Subjects:
Aging
Alzheimer's disease
Amino acids
Amyotrophic Lateral Sclerosis
Cancer
Chromosomes
Clinical trials
Dextromethorphan
Endoplasmic reticulum
Epilepsy
Humans
Huntington Disease
Huntington's disease
Huntingtons disease
Ligands
Medicine
Medicine & Public Health
Motor neuron diseases
Motor neurone disease
Movement disorders
Multiple sclerosis
Neuroblastoma
Neurodegeneration
Neurodegenerative diseases
Neurodevelopmental disorders
Neurodevelopmental Disorders - drug therapy
Neurodevelopmental Disorders - metabolism
Neurological diseases
Neurology
Neurons - metabolism
Neurosciences
Parkinson's disease
Pharmacotherapy
Physiology
Proteins
Psychiatry
Psychopharmacology
Receptors, sigma - metabolism
Receptors, sigma - therapeutic use
Rett syndrome
Review
Review Article
Rivastigmine
Sigma receptors
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Description
Summary:The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.
ISSN:1172-7047
1179-1934
1179-1934
DOI:10.1007/s40263-023-01007-6