Abstract
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.
Highlights
Accepted: 23 February 2022Neurodegenerative diseases (NDDs) are a heterogeneous group of disorders characterized by the progressive dysfunction of the structure and function of neuronal and glial cells and their networks in the central (CNS) and peripheral nervous system
We summarize our knowledge on a novel target for the treatment of NDDs, the activation of the sigma-1 receptor (Sig-1R) for the modulation of elevated immune response by inhibiting chronic inflammation in the CNS
Cytokines and chemokines play a key role in the regulation of the recruitment of specific leukocytes during both the acute and chronic inflammation processes [53]
Summary
Neurodegenerative diseases (NDDs) are a heterogeneous group of disorders characterized by the progressive dysfunction of the structure and function of neuronal and glial cells and their networks in the central (CNS) and peripheral nervous system. Mental abilities generally decline into severe dementia These similarities suggest that therapeutic methods and drugs against one NDD might be applied for the treatment of other diseases as well. We summarize our knowledge on a novel target for the treatment of NDDs, the activation of the sigma-1 receptor (Sig-1R) for the modulation of elevated immune response by inhibiting chronic inflammation in the CNS. This review focuses only on AD, PD, ALS, and HD
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