BDNF Extraction Viewer

Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.

PMID: 41471389 · DOI: 10.3390/ph18121900 · Pharmaceuticals (Basel, Switzerland), 2025 · Noga Gershoni Emek, Andrew M Tan, Michal Geva, Andrea Fekete, Carmen Abate, Michael R Hayden

📄 Abstract

Pridopidine is a highly selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). The S1R is a ubiquitous chaperone protein enriched in the central nervous system and regulates multiple pathways critical for neuronal cell function and survival, including cellular stress responses, mitochondrial function, calcium signaling, protein folding, and autophagy. S1R has a crucial role in the ER mitochondria-associated membrane (MAM), whose dysfunction is implicated in several neurodegenerative diseases. By activating the S1R, pridopidine corrects multiple cellular pathways necessary to the cell's ability to respond to stress, which are disrupted in neurodegenerative diseases. Pridopidine restores MAM integrity; rescues Ca

Confidence: 0.26 · 13 полей извлечено

Идентификация (6 полей)

Target

Sigma-1 receptor

1.00

Alt. target

S1R

1.00

Protein family

Chaperone protein

0.90

Functional class

Chaperone

0.90

Subcellular loc.

ER mitochondria-associated membrane (MAM)

0.90

Isoforms (metab/obesity)

—

0.00

Механизм действия (21 полей)

Mechanism

Pridopidine is a highly selective sigma-1 receptor (S1R) agonist. By activating S1R, it corrects multiple cellular pathways including restoring MAM integrity, rescuing calcium signaling, and modulating stress responses, mitochondrial function, protein folding, and autophagy.

0.95

Mutations (obesity/lean)

—

0.00

Activity (obesity)

—

0.00

Activity temporal

—

0.00

Energy balance

—

0.00

Appetite

—

0.00

Fat metabolism

—

0.00

Lipolysis

—

0.00

Thermogenesis

—

0.00

Muscle metabolism

—

0.00

Inflammation

—

0.00

Glucose metabolism

—

0.00

AA metabolism

—

0.00

Hormonal pathways

—

0.00

Cell death

S1R activation by pridopidine promotes neuronal cell survival by regulating pathways critical for cell function and survival, including cellular stress responses and autophagy.

0.90

Adipocyte fibrosis

—

0.00

Upstream (biochem)

—

0.00

Upstream (physiol)

—

0.00

Downstream (biochem)

S1R activation modulates calcium signaling, mitochondrial function, protein folding, autophagy, and MAM integrity.

0.85

Downstream (physiol)

—

0.00

PTMs

—

0.00

Экспрессия (8 полей)

Tissue expression

ubiquitous, enriched in central nervous system

0.90

In vitro

—

0.00

In vivo

—

0.00

In silico

—

0.00

Genetic association

—

0.00

Ex vivo

—

0.00

Animal model

—

0.00

Diet/model

—

0.00

Клиника (11 полей)

Drug

Pridopidine

1.00

Indication

Huntington's disease and amyotrophic lateral sclerosis

1.00

Patient subgroups

—

0.00

Safety concerns

—

0.00

Off-target

—

0.00

Trial stage

clinical development

0.90

Pharma competitors

—

0.00

AE severity

—

0.00

MOA weight loss

—

0.00

Endpoints

—

0.00

Approved

False

0.90