Suppression of neuroinflammation and composition and method therefor

A method for protecting a nerve cell from neuro-inflammation by promoting the stabilization of Nrf2 protein in glial cells, comprising:

• administering, to a subject, an effective amount of a pharmaceutical composition containing, as an active ingredient, a compound having an inhibiting ability against phosphorylation activity of DYRK1A protein, or a pharmaceutically acceptable salt of the compound,
• wherein
• the compound is a compound expressed by Formulae (I) or (II) shown below:
• where,
• in Formula (I),
• R1 represents a methyl group, an ethyl group, or a propyl group,
• R2 represents a methyl group,
• R3 represents —CH2—CH2— or —CH═CH—, and
• R4 represents a hydrogen atom,
• in Formula (II),
• R5, R6, R7 and R8 independently represent a hydrogen atom, a halogen atom, a carboxyl group, an amino group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms, or a halogen-atom-substituted alkyl group having 1 to 4 carbon atoms, and
• wherein the subject is a patient affected by disease selected from the group consisting of frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and multiple sclerosis.

A method for increasing a post-transplantation settlement rate of a transplanted cell, comprising:

• administering, to a recipient, an effective amount of a pharmaceutical composition, before, simultaneously with, or after transplantation of a cell,
• wherein
• the cell is selected from the group consisting of neuron precursor cell, pluripotent stem cell, and neuron,
• the pharmaceutical composition contains, as an active ingredient, a compound having an inhibiting ability against phosphorylation activity of DYRK1A protein, or a pharmaceutically acceptable salt of the compound, and
• the compound is a compound expressed by Formulae (I) or (II) shown below:
• where,
• in Formula (I),
• R1 represents a methyl group, an ethyl group, or a propyl group,
• R2 represents a methyl group,
• R3 represents —CH2—CH2— or —CH═CH—, and
• R4 represents a hydrogen atom,
• in Formula (II),
• R5, R6, R7 and R8 independently represent a hydrogen atom, a halogen atom, a carboxyl group, an amino group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms, or a halogen-atom-substituted alkyl group having 1 to 4 carbon atoms, and
• wherein the recipient is a patient in need of or receiving the transplantation of the cell, and
• the patient is affected by a neurodegenerative disease selected from the group consisting of infarction of spinal cord, limb paralysis, Parkinson's disease, and Huntington's disease.

A method for increasing a post-transplantation survival rate and/or a post-transplantation retention rate of a transplanted cell, comprising:

• administering, to a recipient, an effective amount of a pharmaceutical composition, before, simultaneously with, or after transplantation of a cell,
• wherein
• the cell is selected from the group consisting of neuron precursor cell, pluripotent stem cell, and neuron,
• the pharmaceutical composition contains, as an active ingredient, a compound having an inhibiting ability against phosphorylation activity of DYRK1A protein, or a pharmaceutically acceptable salt of the compound, and
• the compound is a compound expressed by Formulae (I) or (II) shown below:
• where,
• in Formula (I),
• R1 represents a methyl group, an ethyl group, or a propyl group,
• R2 represents a methyl group,
• R3 represents —CH2—CH2— or —CH═CH—, and
• R4 represents a hydrogen atom,
• in Formula (II),
• R5, R6, R7 and R8 independently represent a hydrogen atom, a halogen atom, a carboxyl group, an amino group, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms, or a halogen-atom-substituted alkyl group having 1 to 4 carbon atoms, and
• wherein the recipient is a patient in need of or receiving the transplantation of the cell, and
• the patient is affected by a neurodegenerative disease selected from the group consisting of infarction of spinal cord, limb paralysis, Parkinson's disease, and Huntington's disease.