Actin-binding protein, Cytoskeletal protein, Extracellular secreted protein (plasma gelsolin), Other (immune modulator, antioxidant protein)
01
Overview
Gelsolin is an actin-binding and actin-severing protein encoded by the GSN gene, present in two isoforms: cytoplasmic and secreted (plasma gelsolin). It has six homologous domains and regulates the actin cytoskeleton by assembling, disassembling, and capping actin filaments, thereby controlling cell shape, motility, and structural integrity. The cytoplasmic form contributes to intracellular architecture and apoptosis inhibition, while plasma gelsolin acts as an extracellular actin scavenger and participates in immune defense and regulation of inflammation. Gelsolin also plays a protective role against oxidative stress, is implicated in clearance of amyloid-beta in Alzheimer’s disease, and is mutated in hereditary amyloidosis leading to pathologic amyloid deposition in tissues. Decreased plasma gelsolin is associated with acute/critical illness, while increased levels are linked to muscle damage or amyloidosis, and gelsolin may function directly or as a marker in neurodegenerative disease and other inflammatory conditions.
Other names
GSNActin-modulating protein gelsolinCytoplasmic gelsolinPlasma gelsolin
02
Mechanism of action
Actin filament capping and severing, leading to regulation of cell shape and motility; Inhibition of apoptosis through mitochondrial stabilization; Binding and solubilization of amyloid-beta, reducing amyloid fibril formation; Anti-inflammatory action by scavenging actin and binding lipopolysaccharides; Antioxidant protection, neutralizing reactive oxygen species; Amyloid clearance
03
Biological functions
Regulation of actin cytoskeleton assembly/disassemblyApoptosis inhibitionScavenger of extracellular actin (clearance system)Regulation of immune response (anti-inflammatory, antibacterial properties)Oxidative stress response (antioxidant protection)Amyloid clearance (anti-amyloidogenic behavior, Alzheimer’s disease)Cell movement and shape regulationBinding bacterial lipopolysaccharide (immune system/inflammation)
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Disease associations
Amyloidosis (hereditary, especially Finnish/Danish types)Neurodegenerative disease (Alzheimer’s disease, Down syndrome)CancerInflammation (e.g., sepsis, liver failure, myocardial infarction, acute respiratory distress syndrome, burns)Other (lattice corneal dystrophy type II)
05
Safety considerations
Therapeutic supplementation of gelsolin could disturb actin homeostasis, potentially impacting cellular structure, motility, and immune responseRisks associated with systemic immune modulation and actin-scavenging activitiesNo clinically proven adverse effects of recombinant gelsolin/infusion therapy yet, as human studies are limited
06
Interacting drugs
There are currently no approved drugs directly targeting gelsolin, but its clearance properties for amyloid beta and research into recombinant gelsolin or plasma gelsolin therapies are under investigation as potential treatments for Alzheimer’s disease and amyloidosis
1 more in the full profile.
07
Biomarkers
Plasma gelsolin levels are used as biomarkers in sepsis, acute inflammation, liver failure, myocardial infarction, and amyloidosis (reductions or elevations indicate disease state/severity)Brain gelsolin levels are proposed as markers for oxidative stress and neurodegenerative progressionAmyloid deposits containing mutated gelsolin protein are biomarkers for hereditary amyloidosis
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