Extracellular proteases and their inhibitors in genetic diseases of the central nervous system.
Cumulative evidence has shown that a delicate balance between serine proteases and their inhibitors is crucial for normal functioning of several biological pathways. The importance of proteases and their inhibitors is well documented in several human diseases. Among them, the best documented are hemophilia B, a genetic deficiency of the serine protease coagulation factor IX and serpinophathies. Alpha-1-antitrypsin deficiency (MIM 107400), is associated with early-onset emphysema and liver disease, while hereditary angioedema (HANE; MIM 106100) is caused by mutations in the C1 inhibitor, a serpin involved in the regulation of the complement cascade. Recently, two human genetic diseases of the central nervous system have been related to mutations in components of extracellular proteolytic systems. Here, we review the recent advances in this field.
Molinari
Florence
F
Départment de Génétique et Unité de Recherche sur les Handicaps Génetiques de l'Enfant, INSERM U393, Hôpital Necker-Enfants Malades, Cedex 15, France. colleaux@necker.fr
Meskanaite
Virginia
V
Munnich
Arnold
A
Sonderegger
Peter
P
Colleaux
Laurence
L
D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D015843:Serpins / Q000235:genetics; D000097522:Neuroserpin
D009479:Neuropeptides; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D000097522:Neuroserpin; C108493:neurotrypsin