Neurotoxic target for amylospheroid, method and material for reducing the neurotoxicity of amylospheroid, and use thereof
AssigneeTao Health Life Pharma Co., Ltd.
InventorMinako HOSHI
Life of this patent
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Abstract
In one or a plurality of embodiments, there is provided a target molecule of amylospheroid, which is expressed in mature neurons and to which the amylospheroid binds to induce death of cells. Further, in one or a plurality of embodiments, there is provided a method and a substance for inhibiting death of mature neurons induced by the amylospheroid. In one aspect, the present disclosure relates to a use of Na+/K+-ATPase α3 as a binding target molecule of amylospheroid. In another aspect, the present disclosure relates to a method for suppressing death of mature neurons induced by the amylospheroid, including inhibiting protein-protein interaction between the amylospheroid and the Na+/K+-ATPase α3, and the like.
Claims39
A use of Na|/K-ATPase α3 as a binding target molecule of amylospheroid inducing death of a mature neuron.
A method for suppressing death of a mature neuron induced by amylospheroid, comprising inhibiting protein-protein interaction between the amylospheroid and Na+/K+-ATPase α3.
A method for suppressing death of a mature neuron induced by amylospheroid, comprising inhibiting at least one calcium channel selected from the group consisting of an N-type voltage-gated calcium channel (VGCC) of a cell membrane, an Na+/Ca2+ exchange transporter of mitochondria (mNCX), a membrane-permeable transition pore of mitochondria (mPTP), and a ryanodine receptor of endoplasmic reticulum (RyR), in the mature neuron interacting with the amylospheroid.
A method for preventing, ameliorating, and/or treating Alzheimer's disease and/or dementia with Lewy bodies, comprising suppressing death of a mature neuron induced by amylospheroid by inhibiting protein-protein interaction between the amylospheroid and Na+/K+-ATPase α3.
A method for preventing, ameliorating, and/or treating Alzheimer's disease and/or Lewy body dementia, comprising inhibiting at least one calcium channel selected from the group consisting of an N-type voltage-gated calcium channel (VGCC) of a cell membrane, an Na+/Ca2+ exchange transporter of mitochondria (mNCX), a membrane-permeable transition pore of mitochondria (mPTP), and a ryanodine receptor of endoplasmic reticulum (RyR), in a mature neuron interacting with amylospheroid.
A method for screening a candidate compound of an effective component of a pharmaceutical composition for preventing, ameliorating, and/or treating Alzheimer's disease and/or dementia with Lewy bodies, comprising:
- measuring an inhibiting capacity of protein-protein interaction between amylospheroid and Na+/K+-ATPase α3 through use of a test compound;
- and
- selecting the candidate compound based on a result of the measurement.
A method for screening a candidate compound of an effective component of a pharmaceutical composition for preventing, ameliorating, and/or treating Alzheimer's disease and/or dementia with Lewy bodies, comprising:
- measuring an inhibiting capacity of protein-protein interaction between amylospheroid and Na+/K+-ATPase α3, and/or binding ability with respect to the amylospheroid, and/or a suppressive capacity with respect to death of a mature neuron induced by the amylospheroid, using a test compound synthesized by performing Structure-Based Drug Design based on a tertiary structure of an extracellular domain 4 of Na+/K+-ATPase α3 or a part thereof;
- and
- selecting the candidate compound based on a result of the measurement.
A method for diagnosing a clinical condition of Alzheimer's disease and/or Lewy body dementia, comprising:
- detecting a signal of an Na+/K+-ATPase α3 imaging probe including a binding partner of Na+/K+-ATPase α3 as a binding portion with respect to the Na+/K+-ATPase α3 from a subject to which the imaging probe has been administered;
- and
- determining severity of a clinical condition of Alzheimer's disease and/or dementia with Lewy bodies based on signal data or image data of the signal or a result of measurement of an Na|/K|-ATPase α3 amount calculated from the signal data or the image data.
A method for checking severity of a clinical condition of Alzheimer's disease and/or dementia with Lewy bodies of a subject, comprising:
- detecting a signal of an Na+/K+-ATPase α3 imaging probe including a binding partner of Na+/K+-ATPase α3 as a binding portion with respect to the Na+/K+-ATPase α3 from the subject to which the imaging probe has been administered;
- and
- measuring an Na+/K+-ATPase α3 amount calculated from signal data or image data of the signal;
- and
- comparing a result of the measurement with a standard in which the severity is determined to be higher as the measured Na+/K+-ATPase α3 amount is lower than an Na+/K+-ATPase α3 amount of a normal individual, and/or the severity is determined to be higher/lower, respectively, in a case where the measured Na+/K+-ATPase α3 amount is higher/lower than a previous Na+/K+-ATPase α3 amount of the subject.
A synthesized, isolated, or purified substance that has binding ability with respect to amylospheroid and is capable of suppressing death of a mature neuron induced by the amylospheroid, and that is similar in structure to an extracellular domain 4 of Na|/K|-ATPase α3 or a part thereof.
A synthesized, isolated, or purified polypeptide, comprising a motif represented by an amino acid sequence of the following Formula (I), (II), or (III):
- (I)
- (SEQ ID NO:
- 7)
- X1X2X3X4
- (II)
- (SEQ ID NO:
- 43)
- X2X3X4X5
- (III)
- (SEQ ID NO:
- 48)
- X2X3X4
- where X1 is arginine (Arg), histidine (His), or lysine (Lys),
- X2 is a hydrophobic amino acid residue or glycine (Gly),
- X3 is asparagine (Asn), glutamine (Gln), serine (Ser), threonine (Thr), cysteine (Cys), histidine (His), or Tyr (tyrosine),
- X4 is tryptophan (Trp), phenylalanine (Phe), or tyrosine (Tyr), and
- X5 is tryptophan (Trp), tyrosine (Tyr), aspartic acid (Asp), or a hydrophobic amino acid residue, the polypeptide having binding ability with respect to amylospheroid.
A diagnosis method for diagnosing a clinical condition of Alzheimer's disease and/or dementia with Lewy bodies, comprising:
- detecting a signal of an amylospheroid imaging probe including a binding partner of amylospheroid as a binding portion with respect to the amylospheroid from a subject to which the imaging probe has been administered;
- and
- determining severity of a clinical condition of Alzheimer's disease and/or dementia with Lewy bodies based on signal data or image data of the signal, or a result of measurement of an amylospheroid amount calculated from the signal data or the image data.
A method for checking severity of a clinical condition of Alzheimer's disease and/or dementia with Lewy bodies of a subject, comprising:
- detecting a signal of an amylospheroid imaging probe including a binding partner of amylospheroid as a binding portion with respect to the amylospheroid from a subject to which the imaging probe has been administered;
- measuring an amylospheroid amount calculated from signal data or image data of the signal;
- and
- comparing a result of the measurement with a standard in which the severity is determined to be higher as the calculated amylospheroid amount is lower than an amylospheroid amount of a normal individual, and/or the severity is determined to be higher/lower, respectively, in a case where the calculated amylospheroid amount is higher/lower than a previous amylospheroid amount of the subject.
Dependencies are inferred from the claim text.