92 results about "STD - Sexually transmitted disease" patented technology

The drug action mechanisms and core techniques of the present invention are summarized in figure 1. Specifically, the invention provides malignant denatured proteins, such as mutant Huntingtin proteinor alpha-synuclein, stick together to grow into oligomer aggregates (1, 2), fibrillar aggregates (3), and ultimately inclusion bodies (4). Young neuronal cells produce a large quantity of Nt-Arg through N-terminal arginylation (5) of endoplasmic reticulum chaperones, such as BiP, and thereafter, arginylated BiP (R-BiP) comes into the cytoplasm and binds with denatured proteins (6). Nt-Arg of R-BiP, as a ligand, binds with the ZZ domain of p62 (7) to induce the structural activation of p62 (8) while the ordinarily closed inactive form of p62 is changed with an open form thereof, and thus PB1 and LC3-binding domains are exposed. On the basis of oligomerization (9) by the PB1 domain, p62 binds with the denatured protein aggregates to be concentrated to autophagically degradable aggregates, that is, p62 bodies (10). Thereafter, p62 completes autophagy targeting (11) and lysosomal proteolysis through binding with LC3 protruding on the autophagosomal membranes. In young neuronal cells, theautophagic proteolysis occurring through steps 5-11 is strong, and thus the cytotoxic protein aggregates (1-5) do not accumulate, but in aged neuronal cells, the autophagic proteolysis occurring through steps 5-11 is weakened, and thus the protein aggregates (1-5) accumulate, resulting in a vicious cycle. The present invention attempts to effectively remove Huntingtin and alpha-synuclein protein aggregates and the like by artificially activating p62 using low-mass ligands of the p62 ZZ domain (12, 13). Specifically, p62 binding the ligands through step 12 promotes p62-R-BiP-denatured protein oligomerization (9) and autophagy aggregate formation (10). In addition, the ligand-62 conjugates step 13 act as autophagy activators (14), to promote LC3 synthesis, the conversion of LC3-I into LC3-II, and the like, thereby promoting the formation of autophagosomes (15).

The present invention relates to compositions and methods for treating diseases and / or disorders associated with protein aggregates. By expressing a chimeric antigen receptor (CAR) in a monocyte, macrophage or dendritic cell, the modified cell is recruited or applied to the tissue microenvironment where it acts as a potent immune effector by infiltrating the tissue and eliminating, reducing, inhibiting or preventing protein aggregation. Other aspects of this invention include methods and pharmaceutical compositions comprising the CAR modified monocyte, macrophage or dendritic cell for treatinga condition, such as a neurodegenerative disease / disorder, an inflammatory disease / disorder, a cardiovascular disease / disorder, a fibrotic disease / disorder and amyloidosis.

The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted,4-alkylidenyl piperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and / or leukotriene component. These conditions include preferably asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.