Method of effecting neuroprotection using soluble Neuregulin isoforms
The present invention refers to soluble Neuregulin-1 isoforms representing Posttranslational Neuregulin-1 modifications as medication in cognition-related neurological disorders, in particular schizophrenia, Alzheimer's and Parkinson's diseases.
1. A method of treating a subject suffering from Parkinson's disease, comprising systemically administering to said subject a recombinant soluble Type I Neuregulin-1 β isoform which is an about 15 to about 35 kD N-terminal fragment of Type I Neuregulin-1 β, wherein said recombinant soluble Type I Neuregulin-1 β isoform is the first 245, 246, 247, 248, 249, or 250 amino acids of Type I Neuregulin-1 β.
2. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is the first 245 amino acids of Type I Neuregulin-1 β.
3. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform crosses the blood-brain barrier.
4. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform reduces dopaminergic cell death in said subject compared to a subject that is not treated with said recombinant soluble Type I Neuregulin-1 β isoform.
5. The method of claim 1 , wherein the Type I Neuregulin-1 β isoform has an isoelectric point (pI) of about 4 to about 10.
6. The method of claim 1 , wherein the Type I Neuregulin-1 β isoform is a modified polypeptide, wherein the modifications are selected from phosphorylation, glycosylation, methylation, myristoylation, oxidation and any combination thereof.
7. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of 3 to 600 ng/kg body weight of the subject to be treated.
8. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of 150 to 300 ng/kg body weight of the subject to be treated.
9. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of about 3, 5, 20, 50, 150, 200, 300 or 600 ng/kg body weight of the subject to be treated.
10. The method of claim 1 , wherein said recombinant soluble Type I Neuregulin-1 β isoform is administered in an amount of about 20 ng/kg body weight of the subject to be treated.
11. The method of claim 1 , wherein the administration is by intravenous or intraperitoneal injection.