title: Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: relationship to S-100B levels and blood-brain barrier function.
abstract: BACKGROUND
  Preliminary studies report on significantly higher levels of the major cytoskeleton protein actin in CSF of patients with neurodegenerative conditions and that the dynamics of these levels obviously correlates with disease progression and clinical disability. One of the primary functions of actinfree Gc-Globulin is to bind and neutralize extracellular monomeric actin, released into the circulation by necrotic or ruptured cells, and thus ameliorating the clinical outcome in situations of severe organ damage.
  
  
  OBJECTIVE
  This is the first study to investigate actinfree Gc-Globulin and S100-B levels (as reliable marker of neurodegeneration) in paired CSF and serum samples of patients with multietiological CNS diseases.
  
  
  RESULTS
  42% of all patients with CNS disease displayed serum concentrations of actinfree Gc-Globulin above the established reference range. CSF concentrations of actinfree Gc-Globulin and S100-B were positively correlated with the severity of blood-brain barrier (BBB) dysfunction. Furthermore, patients with severe BBB dysfunction presented a higher percentage of intrathecal synthesis of actinfree Gc-Globulin compared to patients with mild to moderate dysfunction and to patients with normal BBB function. Representative longitudinal data from selected patients demonstrated an inverse behaviour of actinfree Gc-Globulin and S100-B CSF concentrations, suggesting a consumption of the actin scavenger capacity of Gc-Globulin in times of increased neuronal damage. This presumption was supported by the fact that those conditions associated with a severe neuronal damage, in particular CNS trauma, and highest S100-B concentrations simultaneously displayed lowest actinfree Gc-Globulin levels, and thus residual actin binding capacity of Gc-Globulin.
  
  
  CONCLUSIONS
  In summary, our data propose a function of actinfree Gc-Globulin also in the clearance of actin filaments from CSF of patients with neuronal damage. However, active recruitment of hepatic derived actinfree Gc-Globulin to the site of CNS injury is not observed. Much more, BBB leakage enables extraneuronally synthesized actinfree Gc-Globulin to extent its scavenger capacity for actin also to the subarachnoidal space. Furthermore, intrathecal synthesis of actinfree Gc-Globulin seems to be increased in patients with severe neurodegeneration.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, Aachen, Germany. ogressner@ukaachen.de
authors.forename: Olav A
authors.initials: OA
authors.lastname: Gressner
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Schifflers
authors.forename: Philipp
authors.initials: P
authors.lastname: Kim
authors.forename: Leo
authors.initials: L
authors.lastname: Heuts
authors.forename: Birgit
authors.initials: B
authors.lastname: Lahme
authors.forename: Axel M
authors.initials: AM
authors.lastname: Gressner
mesh_terms: D000199:Actins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood* / Q000134:cerebrospinal fluid*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood* / Q000134:cerebrospinal fluid*; D013997:Time Factors; D016896:Treatment Outcome; D014809:Vitamin D-Binding Protein / Q000096:biosynthesis / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D000199:Actins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014809:Vitamin D-Binding Protein