JP2006519189A5 - - Google Patents

Claims (16)

  An antagonist of hsgk1 protein or hsgk3 protein for the treatment and / or prevention of cataract, glaucoma or diabetic neuropathy, said antagonist being structurally similar to the natural substrate of hsgk1 protein or hsgk3 protein, Alternatively, a medicament comprising a negative regulator of transcription of the hsgk1 gene or the hsgk3 gene.   The medicament comprising an antagonist of the hsgk1 protein or the hsgk3 protein according to claim 1, wherein the antagonist is structurally similar to the phosphorylating amino acid serine or threonine.   Method for diagnosing a predisposition to develop cataract, glaucoma and / or diabetic neuropathy by the use of a single or double stranded nucleic acid comprising a sequence of a human homologue of the hsgk family or one of its fragments .   The method according to claim 3, characterized in that the single-stranded or double-stranded nucleic acid comprises the sequence of the hsgk1 gene described in accession number NM005627, or one of its fragments.   Method according to claim 4, characterized in that the hsgk1 gene comprises at least one polymorphic nucleotide, in particular the "SNP" of the hsgk1 gene.   The polymorphic nucleotide of the hsgk1 gene contains a G insertion at position 732/733 in intron 2 of the hsgk1 gene, a T / C substitution at position 2071 in intron 6 of the hsgk1 gene, and position 2617 in exon 8 of the hsgk1 gene. 6. The method of claim 5, wherein the method is selected from the group consisting of:   The method according to claim 3, characterized in that the single-stranded or double-stranded nucleic acid comprises the sequence of the hsgk3 gene described in Accession No. AF169035, or one of its fragments.   8. The method according to claim 7, characterized in that the hsgk3 gene comprises at least one polymorphic nucleotide of the hsgk3 gene, in particular “SNP”.   Detecting the phosphorylation of a substrate of a human homologue of the sgk family by use of an antibody against an epitope of the substrate comprising a phosphorylation site wherein the antibody is either phosphorylated or non-phosphorylated A method for diagnosing a predisposition to develop at least one of the following diseases: cataract, glaucoma and diabetic neuropathy.   10. The method according to claim 9, wherein the substrate of the human homologue of the sgk family is Nedd4-2 (Accession No. BAA23711).   A kit for diagnosing one of the diseases which are cataract, glaucoma and diabetic neuropathy, comprising an antibody against hsgk1 or hsgk3, or under stringent conditions, the hsgk1 gene described in Accession No. NM005627, Alternatively, the above kit comprising a nucleic acid capable of hybridizing with the hsgk3 gene described in Accession No. AF169035, or a combination of these antibodies and nucleic acid.   The nucleic acid, under stringent conditions, includes the polymorphic nucleotide of the hsgk1 gene or hsgk3 gene, particularly the “sNP”, the hsgk1 gene described in Accession No. NM005627, or the DNA region of the hsgk3 gene described in Accession No. AF16935 The kit according to claim 11, which can hybridize with the kit. A screening method for identifying and characterizing a substance having a therapeutic activity from among a large number of test substances, wherein the substance having a therapeutic activity is selected from the group consisting of cataract, glaucoma and diabetic neuropathy Is used to treat and / or prevent at least one of the following steps:
a) heterogeneously co-expressing the following in the cell:
i) the glucose transporter Glut1, and
ii) hsgk1 and / or hsgk3,
b) in each case culturing at least one of the aliquots A ₁ -A _x of the cells in the presence of at least one test substance, wherein at least one test substance is in each case , And culturing an aliquot B of control cells in the absence of any test substance,
c) measuring the activity of the glucose transporter Glut1 in the aliquots A _{1 to} A _x of the cells compared to the activity of the glucose transporter Glut1 in the aliquot B of the control cells;
Including the above method. In step a), the hsgk1 substrate Nedd4-2 is co-expressed in addition to or in conjunction with the glucose transporter Glut1, and in step c) the hsgk1 substrate Nedd4- in cell aliquots A ₁ -A _x . 14. The screening method according to claim 13, wherein the degree of phosphorylation of 2 (Accession No. BAA23711) is measured in comparison with aliquot B of control cells. A screening method for identifying and characterizing a substance having a therapeutic activity from among a large number of test substances, wherein the substance having a therapeutic activity is selected from the group consisting of cataract, glaucoma and diabetic neuropathy Is used to treat and / or prevent at least one of the following steps:
a) heterogeneously co-expressing in at least one of cell aliquots A ₁ -A _x :
i) the glucose transporter Glut1, and
ii) hsgk1 and / or hsgk3,
and,
Heterologously expressing in at least one of aliquots B ₁ -B _x of cells:
i) Glucose transporter Glut1,
In case b), respectively, in the presence of at least one test substance, at least one test material of step (here culturing aliquots A ₁ to A _x and B ₁ .about.B _x cells, respectively In some cases, corresponding to the index 1-X of the aliquot of cells),
c) comparing and measuring the activity of the glucose transporter Glut1 in cell aliquots A ₁ -A _x and cell aliquots B ₁ -B _x ,
Including the above method. In step a), the hsgk1 substrate Nedd4-2, in addition to or instead of the glucose transporter Glut1, is associated with both cell aliquots A ₁ -A _x and cell aliquots B ₁ -B _x. is expressed, in step c), the degree of phosphorylation of hsgk1 substrate Nedd4-2 (accession number BAA23711) in aliquots a ₁ to a _x of the cells is measured by comparing with an aliquot B ₁ .about.B _x cell, The screening method according to claim 15.