Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

The present disclosure is concerned with 2-aminoaryl-5-aryloxazole compounds that are capable of activating NF-κB signaling. The present disclosure is also concerned with methods of using these compounds for the treatment of neurological disorders such as, for example, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, spinal muscular atrophy, traumatic brain injury, vascular dementia, Huntington's disease, mental retardation, and attention deficit and hyperactivity disorder (ADHD), and neuromuscular disorders such as, for example, Duchenne muscular dystrophy (DMD). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Provided herein are optionally substituted benzoimidazol-1,2-yl amides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating Kv7 associated diseases, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania and tinnitus with such compounds and pharmaceutical compositions.

The present invention pertains to a) beta-lactoglobulin or b) a nutritional composition comprising beta-lactoglobulin for use in preventing and/or treating a metabolic disorder and/or muscle atrophy. It also pertains to a method of preventing and/or treating a metabolic disorder and/or muscle atrophy in a subject. It furthermore pertains to use of a) beta-lactoglobulin or b) a nutritional composition comprising beta-lactoglobulin for increasing the level of insulin and/or glucagon in the blood of a subject and the present invention also pertains to a non-therapeutic use or method of a) beta-lactoglobulin orb) a nutritional composition comprising BLG. It also pertains to beta-lactoglobulin (BLG) for use in preventing and/or treating diabetes or prediabetes in a subject. It furthermore pertains to a nutritional composition for use in preventing and/or treating diabetes or prediabetes in a subject.

The present invention pertains to a) beta-lactoglobulin or b) a nutritional composition comprising beta-lactoglobulin for use in preventing and/or treating a metabolic disorder and/or muscle atrophy. It also pertains to a method of preventing and/or treating a metabolic disorder and/or muscle atrophy in a subject. It furthermore pertains to use of a) beta-lactoglobulin or b) a nutritional composition comprising beta-lactoglobulin for increasing the level of insulin and/or glucagon in the blood of a subject and the present invention also pertains to a non-therapeutic use or method of a) beta-lactoglobulin orb) a nutritional composition comprising BLG. It also pertains to beta-lactoglobulin (BLG) for use in preventing and/or treating diabetes or prediabetes in a subject. It furthermore pertains to a nutritional composition for use in preventing and/or treating diabetes or prediabetes in a subject.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Dysregulation of TAF1 function by various mechanisms can lead to disease in the central nervous system, such as the TAF1 Intellectual Disability (ID) Syndrome which currently has no therapeutic treatments. The present invention indicates that a novel T-type calcium channel enhancer, such as SAK3, has disease-modifying effects in animal models of TAF1 editing. In addition, the present invention provides insights into the molecular mechanism by which SAK3 exerts in pharmacologic effects. Moreover, the present findings imply that the T-Type voltage-gated calcium channels are novel molecular targets to develop therapeutics to treat TAF1 ID syndrome and that SAK3 is an attractive drug candidate to treat TAF1 associated neurologic disorders.

CB-7 exhibits a weak TLR7 inhibiting effect in normal mice. The present invention provides a novel compound with a stronger TLR7 inhibiting effect than CB-7, a pharmaceutically acceptable salt of said compound, or a prodrug of said compound or salt. The present invention also provides a drug for the prevention or treatment of diseases associated with the activation of TLR7, said drug including the aforementioned TLR7 activation inhibitor.

A composition suitable for diagnosing a musculoskeletal disease and a composition suitable for preventing or treating a musculoskeletal disease are disclosed. The composition contains zinc finger protein with KRAB and SCAN domains 8 (Zkscan8) protein, which can be effectively used as an excellent biomarker for obtaining accurate information about the occurrence and progression stages of a musculoskeletal disease, specifically a tendon disease or a ligament disease. The compositions containing Zkscan8 can be effectively used for preventing or treating a musculoskeletal disease through Zkscan8 overexpression.