Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands.
Ferenc BogárLivia FulopBotond PenkePublished in: Biomolecules (2022)
Neurodegenerative diseases (NDDs) are characterized by progressive deterioration of the structure and function of cells and their networks in the nervous system. There are currently no drugs or other treatments that can stop the progression of NDDs. NDDs have many similarities and common pathways, e.g., formation of misfolded amyloid proteins, intra- and extracellular amyloid deposits, and chronic inflammation. Initially, the inflammation process has a cytoprotective function; however, an elevated and prolonged immune response has damaging effects and causes cell death. Neuroinflammation has been a target of drug development for treating and curing NDDs. Treatment of different NDDs with non-steroid anti-inflammatory drugs (NSAIDs) has failed or has given inconsistent results. The use of NSAIDs in diagnosed Alzheimer's disease is currently not recommended. Sigma-1 receptor (Sig-1R) is a novel target for NDD drug development. Sig-1R plays a key role in cellular stress signaling, and it regulates endoplasmic reticulum stress and unfolded protein response. Activation of Sig-1R provides neuroprotection in cell cultures and animal studies. Clinical trials demonstrated that several Sig-1R agonists (pridopidine, ANAVEX3-71, fluvoxamine, dextrometorphan) and their combinations have a neuroprotective effect and slow down the progression of distinct NDDs.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- anti inflammatory drugs
- oxidative stress
- cell death
- cerebral ischemia
- immune response
- clinical trial
- cell cycle arrest
- lipopolysaccharide induced
- traumatic brain injury
- signaling pathway
- cognitive impairment
- lps induced
- multiple sclerosis
- single cell
- brain injury
- cognitive decline
- randomized controlled trial
- binding protein
- dendritic cells
- blood brain barrier
- inflammatory response
- stem cells
- toll like receptor
- drug induced
- small molecule
- stress induced
- phase iii
- amino acid
- double blind
- protein protein