Disclosed is a method for identifying inhibitors of the interaction of CD36 receptor and amyloid-beta protein (Aβ), which consists in: immobilizing CD36 on a polystyrene plate; and detecting by colorimetric, the interaction thereof with fibrillar Aβ (fAβ), using a polyclonal anti-Aβ antibody and a secondary antibody conjugated to horseradish peroxidase (HRP). The inhibitors identified are potential agents for the treatment of Alzheimer's disease.

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.

The invention relates to the field of biomedical and pharmacological research, in particular in the field of immunology, allergies, cancers, bone diseases and autoimmune diseases. The invention is based on the recent finding that SWAP-70 dimerizes, that the dimerization takes place via a specific, largely unique and limited region of the protein, and that this dimerization is central to the function of the protein (and probably the stability thereof). The invention provides a screening method which makes it possible to identify new active ingredients which, by accumulating at the dimerization domain and inhibiting SWAP-70 activity, suppress the supporting function of SWAP-70 in tumorigenesis, tumor cell migration and invasion, bone-degrading osteoclast activity, and the allergic reaction, as well as in autoimmune diseases. The object is achieved by a method for identifying a substance which inhibits the activity of SWAP-70, wherein the method comprises the following: contacting at least one test substance with SWAP-70, detecting the degree of dimerization of SWAP-70, selecting a test substance which inhibits the dimerization of SWAP-70.

In one aspect, the present invention provides a method of selecting or identifying an agent that inhibits a target protein having an active site. In another aspect, the invention provides a method of selecting an agent that inhibits a target protein having an active site for further optimization. In some embodiments, the methods comprise measuring or predicting stability of an induced fit conformation of an agent contacted to an active site of the protein, wherein the agent is selected if the stability of the induced fit conformation of the agent contacted to the active site of the protein is increased relative to a reference stability.

A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.

The present invention features the use of compstatin and complement inhibiting analogs thereof for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, choroidal neovascularization, and/or retinal neovascularization. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a second therapeutic agent. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a gel-forming material, e.g., soluble collagen, and methods of administering the compositions.

Aspects of the present disclosure include amyloid β (Aβ) peptides. In certain aspects, the Aβ peptides include a chiral substitution at an electrostatic cluster amino acid residue. Also provided are compositions, non-human animals, and kits that include the Aβ peptides. Methods involving the Aβ peptides are also provided.

The present disclosure provides methods of identifying a candidate agent for treating an apoE-associated neurodegenerative disorder. The methods involve contacting a PCSK1 or a PCSK2 polypeptide with an apolipoprotein E polypeptide in the presence of a test agent.

In certain aspects, the invention provides a method for treating a disease or condition in a subject, the method comprising co-administering to a subject in need thereof a therapeutically effective amount of at least one ULK1-inhibiting pyrimidine, and a therapeutically effective amount of an mTOR inhibitor.

The present inventors discovered that problems of existing antibody pharmaceuticals can be solved by producing antigen-binding molecules that contain an antigen-binding domain whose antigen-binding activity varies depending on the concentration of a target tissue-specific compound. Use of antigen-binding molecules of the present invention enables various diseases that originate from a target tissue to be treated in a manner specific to the target tissue.