title: beta2-Microglobulin is potentially neurotoxic, but the blood brain barrier is likely to protect the brain from its toxicity.
abstract: BACKGROUND
  In dialysis-related amyloidosis, beta2-microglobulin accumulates as amyloid fibrils preferentially around bones and tendons provoking osteoarthritis. In addition to the pathologic role played by the amyloid fibrils, it can be speculated that a pathogenic role is also played by the high concentrations of soluble beta2-microglobulin because it is toxic for certain cell lines like HL60 and mitogen for other cells such as the osteoclasts. The discovery that beta2-microglobulin can influence the biology of certain cells may lead to the assumption that it might affect neuronal cells that are quite sensitive to amyloidogenic proteins in the oligomeric state. Such a concern might be supported by clinical evidence that haemodialysis is associated with the risk of a cognitive impairment.
  
  
  METHODS
  The cytotoxicity of beta2-microglobulin on the SH-SY5Y neuroblastoma cells was assayed by the MTT test. The beta2-microglobulin concentration was determined in the cerebrospinal fluid of four different patients by means of immunonephelometry and western blot.
  
  
  RESULTS
  Oligomeric beta2-microglobulin is cytotoxic for the SH-SY5Y cells at a concentration that can be easily reached in the plasma of patients on haemodialysis. However, the beta2-microglobulin concentration, measured in the cerebrospinal fluid of a haemodialysis patient, appears to be independent of its plasma concentration and is maintained under the lower limit of cytotoxicity we have determined in the cell culture.
  
  
  CONCLUSIONS
  Although beta2-microglobulin is potentially neurotoxic, it is unlikely that this protein plays a role in the pathophysiology of cognitive impairment observed in haemodialysis patients due to the protective effect of the blood brain barrier that maintains a low concentration of beta2-microglobulin in the cerebrospinal fluid.
authors.affiliation: Dipartimento di Biochimica, via Taramelli 3b, 27100 Pavia, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.forename: Silvia
authors.initials: S
authors.lastname: Cassinelli
authors.forename: Monica
authors.initials: M
authors.lastname: Bucciantini
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
authors.forename: Gina
authors.initials: G
authors.lastname: Gregorini
authors.forename: Giulia
authors.initials: G
authors.lastname: Albonico
authors.forename: Remigio
authors.initials: R
authors.lastname: Moratti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montagna
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
mesh_terms: D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain; D045744:Cell Line, Tumor; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D009447:Neuroblastoma; D006435:Renal Dialysis / Q000009:adverse effects; D001613:beta 2-Microglobulin / Q000009:adverse effects* / Q000502:physiology
chemical_list: D001613:beta 2-Microglobulin