Functional role and potential therapeutic use of Reelin, Gas6 and Protein S in relation to adult neural stem or progenitor cells

A method of modulating the activity of a Reelin receptor, Gas 6 receptor, a Protein S receptor or a combination thereof, on a neural stem cell or neural progenitor cell, the method comprising exposing the cell expressing the receptor to exogenous reagent, antibody, or affibody, wherein the exposure induces or inhibits the neural stem cell or neural progenitor cell to proliferate, differentiate or survive.

A method for reducing a symptom of a disease or disorder of the central nervous system in a mammal in need of such treatment comprising administering Reelin, Gas6, Protein S, a molecule that regulates the phosphorylation status of Dab1 or a Reelin, Gas6 or Protein S agonist or antagonist to the mammal.

A method for inducing the in situ proliferation, differentiation or survival of a neural stem cell or neural progenitor cell located in the neural tissue of a mammal, the method comprising administering a therapeutically effective amount of Reelin, Gas6, Protein S or a molecule that regulates the phosphorylation status of Dab1 to the neural tissue to modulate the proliferation, differentiation or survival of the cell.

A method for accelerating the growth of neural stem cells or neural progenitor cells in a desired target tissue in a subject, comprising administering to the subject an expression vector containing a Reelin, Gas6 or Protein S gene in a therapeutically effective amount.

A method of enhancing neurogenesis in a patient suffering from a disease or disorder of the central nervous system, by infusion of Reelin, Gas6, Protein S, a molecule that causes the regulates the phosphorylation status of Dab1 or a Reelin, Gas6 or Protein S receptor agonist or antagonist.

A method of alleviating a symptom in a patient suffering from a disease or disorder of the central nervous system by enhancing neurogenesis through infusion of Reelin, Gas6, Protein S, a molecule that regulates the phosphorylation status of Dab1 or a Reelin, Gas6 or Protein S receptor agonist or antagonist.

A method for producing a population of cells enriched for human neural stem cells or human neural progenitor cells, comprising:

• a. contacting a population containing neural stem cells or neural progenitor cells with a reagent that recognizes a determinant on a Reelin receptor, Gas6 receptor or Protein S receptor;
• and
• b. selecting for cells in which there is contact between the reagent and the determinant on the surface of the cells of step (a), to produce a population highly enriched for central nervous system stem cells.

A method of reducing a symptom of a disease or disorder of the central nervous system in a subject comprising the steps of administering into the spinal cord of the subject a composition comprising a population of isolated neural stem cells or neural progenitor cells obtained from fetal or adult tissue;

• and Reelin, Gas6, Protein S, a molecule that regulates the phosphorylation status of Dab1 or a Reelin, Gas6 or Protein S agonist or antagonist or a combination thereof such that the symptom is reduced.

A method of gene delivery and expression in a target cell of a mammal, comprising the step of introducing a viral vector into the target cell, wherein the viral vector has at least one insertion site containing a nucleic acid which encodes Reelin, Gas6, Protein S, a Reelin receptor, a Gas6 receptor or a Protein S receptor, the nucleic acid gene operably linked to a promoter capable of expression in the host.

A method for alleviating a symptom of a disease or disorder of the central nervous system in a patient comprising the steps of:

• (a) providing a population of neural stem cells or neural progenitor cells;
• (b) suspending the neural stem cells or neural progentor cells in a solution comprising Reelin, Gas6, Protein S or a molecule that regulates the phosphorylation status of Dab1 or a combinatin thereof to generate a cell suspension;
• (c) delivering the cell suspension to an injection site in the central nervous system of the patient to alleviate the symptom.

A method of modulating a Reelin, Gas6 or Protein S receptor or a Reelin, Gas6 or Protein S ligand on the surface of a neural stem cell or neural progenitor cell comprising the step of contacting the cell expressing the receptor, or ligand to exogenous reagent, antibody, or affibody, wherein the exposure induces or inhibits the neural stem cell or neural progenitor cell to proliferation, differentiation or survival.

A method of determining an isolated candidate Reelin, Gas6 or Protein S receptor modulator compound for its ability to modulate neural stem cell or neural progenitor cell activity comprising the steps of:

• (a) administering the isolated candidate compound to a non-human mammal;
• and
• (b) determining if the candidate compound has an effect on modulating the neural stem cell or neural progenitor cell activity in the non-human mammal.