Abstract: An object of the present invention is to provide an agent for preventing or treating frontotemporal lobar degeneration which does not cause noticeable adverse reactions and exhibits an excellent effect of preventing and treating frontotemporal lobar degeneration caused by different factors. In the present invention, a human monoclonal antibody that specifically binds to human HMGB1, which comprises heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 each consisting of a specific amino acid sequence and light chain CDR1, light chain CDR2, and light chain CDR3 each consisting of a specific amino acid sequence, can be used as an agent for preventing or treating frontotemporal lobar degeneration.

Abstract: It has been revealed that, from a pre-onset stage of Alzheimer's disease, enhancement of phosphorylations of MARCKS and the like causes abnormal spine formation or the like, consequently developing the disease. It also has been revealed that the phosphorylations of MARCKS and the like are caused by PKC and the like, and further that b-raf is involved in phosphorylation of tau protein important for the progression of Alzheimer's disease. Thus, these proteins have been found to be target molecules useful in the diagnosis and treatment of Alzheimer's disease. In addition, it has also been revealed that, in a pre-onset stage of frontotemporal lobar degeneration, b-RAF phosphorylation enhancement causes a decrease in the number of spines and the like, consequently developing the disease. Thus, b-RAF has been found to be a target molecule useful in the diagnosis and treatment of frontotemporal lobar degeneration.

Abstract: It has been revealed that, from a pre-onset stage of Alzheimer's disease, enhancement of phosphorylations of MARCKS and the like causes abnormal spine formation or the like, consequently developing the disease. Moreover, it has also been revealed that the phosphorylations of MARCKS and the like are caused by PKC and the like, and further that b-raf is involved in the phosphorylation of a tau protein important for the progression of Alzheimer's disease. Thus, these proteins have been found to be target molecules useful in the diagnosis and treatment of Alzheimer's disease. In addition, it has also been revealed that, pre-onset in a stage of frontotemporal lobar degeneration also, b-RAF phosphorylation enhancement causes a decrease in the number of spines and the like, consequently developing the disease. Thus, b-RAF has been found to be a target molecule useful in the diagnosis and treatment of frontotemporal lobar degeneration.

Abstract: It is an object of the present invention to provide a human monoclonal antibody that has a high inhibitory activity on phosphorylation of Ser46 of human MARCKS and binds specifically to human HMGB1, and a pharmaceutical composition or the like for treating or preventing Alzheimer's disease, containing the antibody as an active component. A human monoclonal antibody that binds specifically to human HMGB1 and contains a heavy-chain CDR1, a heavy-chain CDR2, and a heavy-chain CDR3 consisting of specific amino acid sequences and a light-chain CDR1, a light-chain CDR2, and a light-chain CDR3 consisting of specific amino acid sequences is used. The human monoclonal antibody can also be used as a pharmaceutical composition for treating or preventing Alzheimer's disease.

Abstract: An object of the present invention is to provide a substance that can prevent or treat mild cognitive impairment. Mammalian YAP, a polynucleotide encoding mammalian YAP, or a substance capable of increasing an amount of mammalian YAP in a nucleus of a brain neuron is used in the prevention or treatment of mild cognitive impairment.

Abstract: An object of the present invention is to provide a novel therapeutic agent for frontotemporal lobar degeneration. The present invention provides a therapeutic agent for frontotemporal lobar degeneration containing an active ingredient which suppresses gene expression or protein function of Gas6 and/or Tyro3. The active ingredient may contain a nucleic acid.

Abstract: To provide a compound which enables treatment or prevention of spinocerebellar ataxia, analyses were carried out based on a screening using a spinocerebellar ataxia type 1 (SCA1) fly model and on the like. As a result, the following proteins ameliorating the pathology of spinocerebellar ataxia were identified: RPA1, PNKP, XRCC3, XRCC4, CCNH, POLE, POLH, and PER1. On the other hand, the following proteins aggravating the pathology were identified: CHK1, LIG3, FEN1, LIG1, ERCC5, XAB2, ERCC2, DMC1, RECQL5, MUS81, EME1, SPO11, and BLM. In addition, it has been revealed that ATXN1, which is a cause of SCA1, binds to RPA1, BRCA1, and BRCA2, and suppresses the activities of these proteins, so that the above-described pathology is caused.

Abstract: Provided is a method for detecting a neurodegenerative disease selected from the group consisting of human Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) with high sensitivity and high specificity.

Abstract: An anti-HMGB1 antibody comprising a light chain variable region comprising complementarity-determining regions or the like including amino acid sequences of SEQ ID NOs: 4 to 6, and a heavy chain variable region comprising complementarity-determining regions or the like including amino acid sequences of SEQ ID NOs: 10 to 12, or an anti-HMGB1 antibody comprising a light chain variable region or the like comprising an amino acid sequence of SEQ ID NO: 3, and a heavy chain variable region comprising an amino acid sequence or the like of SEQ ID NO: 9, and a composition for treating or preventing Alzheimer's disease, comprising the same as an active ingredient.

Abstract: An anti-HMGB1 antibody comprising a light chain variable region comprising complementarity-determining regions or the like including amino acid sequences of SEQ ID NOs: 4 to 6, and a heavy chain variable region comprising complementarity-determining regions or the like including amino acid sequences of SEQ ID NOs: 10 to 12, or an anti-HMGB1 antibody comprising a light chain variable region or the like comprising an amino acid sequence of SEQ ID NO: 3, and a heavy chain variable region comprising an amino acid sequence or the like of SEQ ID NO: 9, and a composition for treating or preventing Alzheimer's disease, comprising the same as an active ingredient.

Abstract: It has been revealed that, from a pre-onset stage of Alzheimer's disease, enhancement of phosphorylations of MARCKS and the like causes abnormal spine formation or the like, consequently developing the disease. Moreover, it has also been revealed that the phosphorylations of MARCKS and the like are caused by PKC and the like, and further that b-raf is involved in the phosphorylation of a tau protein important for the progression of Alzheimer's disease. Thus, these proteins have been found to be target molecules useful in the diagnosis and treatment of Alzheimer's disease. In addition, it has also been revealed that, in a pre-onset stage of frontotemporal lobar degeneration also, b-RAF phosphorylation enhancement causes a decrease in the number of spines and the like, consequently developing the disease. Thus, b-RAF has been found to be a target molecule useful in the diagnosis and treatment of frontotemporal lobar degeneration.

Abstract: To provide a compound which enables treatment or prevention of spinocerebellar ataxia, analyses were carried out based on a screening using a spinocerebellar ataxia type 1 (SCA1) fly model and on the like. As a result, the following proteins ameliorating the pathology of spinocerebellar ataxia were identified: RPA1, PNKP, XRCC3, XRCC4, CCNH, POLE, POLH, and PERI. On the other hand, the following proteins aggravating the pathology were identified: CHK1, LIG3, FEN1, LIG1, ERCC5, XAB2, ERCC2, DMC1, RECQL5, MUS81, EME1, SPO11, and BLM. In addition, it has been revealed that ATXN1, which is a cause of SCA1, binds to RPA1, BRCA1, and BRCA2, and suppresses the activities of these proteins, so that the above-described pathology is caused.

Abstract: To provide a novel protein that can be a preventive/remedy in neurodegenerative diseases such as polyglutamine diseases based on the finding obtained by revealing the relationship between transcriptional dysfunction and neuronal death. Disclosed is a protein that is one of the following proteins (a) and (b). (a) A protein including an amino acid sequence represented by any one of SEQ ID NOS: 1 to 3. (b) A protein including an amino acid sequence in which one to several amino acids are deleted, substituted or added in the amino acid sequence of (a), the protein having a dominant negative effect on a transcriptional activation factor YAP.

Abstract: To provide a prophylactic/therapeutic agent for neurodegenerative diseases (such as polyglutamine diseases), the agent containing an HMGB family protein or a derivative thereof, such as a protein according any one of (a) and (b) below: (a) a protein having the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8; and (b) a protein having an amino acid sequence resulting from deletion, substitution, addition or insertion of one or more amino acids in the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8 and having binding activity to an abnormal polyglutamine protein produced in a neurodegenerative disease.

Abstract: To provide a prophylactic/therapeutic agent for neurodegenerative diseases (such as polyglutamine diseases), the agent containing an HMGB family protein or a derivative thereof, such as a protein according any one of (a) and (b) below: (a) a protein having the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8; and (b) a protein having an amino acid sequence resulting from deletion, substitution, addition or insertion of one or more amino acids in the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8 and having binding activity to an abnormal polyglutamine protein produced in a neurodegenerative disease.

Abstract: To provide a novel protein that can be a preventive/remedy in neurodegenerative diseases such as polyglutamine diseases based on the finding obtained by revealing the relationship between transcriptional dysfunction and neuronal death. Disclosed is a protein that is one of the following proteins (a) and (b). (a) A protein including an amino acid sequence represented by any one of SEQ ID NOS: 1 to 3. (b) A protein including an amino acid sequence in which one to several amino acids are deleted, substituted or added in the amino acid sequence of (a), the protein having a dominant negative effect on a transcriptional activation factor YAP.