Abstract: Pharmaceutical compounds, compositions, methods, and uses therefor are presented using selected triazolopyridines and triazolopyrimidines to inhibit or reduce phosphorylation of tau proteins or that act as antagonists of corticotropin-releasing factor. Viewed from another perspective, compounds, compositions, and methods are presented for treating or preventing symptoms of Alzheimer's disease by inhibiting or reducing the phosphorylation of tau proteins.

Abstract: This invention provides synthetic exosomes that contain and deliver an effective amount of a gene editor. In certain embodiments the synthetic exosome comprises a liposome formed from a lipid bilayer, where said lipid bilayer comprises: one or more phospholipids selected from the group consisting of phosphate lipids, phosphoglycerol lipids, phosphocholine lipids, and phosphoethanolamine lipids where the lipid carbon chain ranges from 3 to 24 carbon atoms: cholesterol, a cholesterol derivative, or a phytosterol; and a non-ionic surfactant; where the lipid bilayer does not contain an alcohol: the exosome is less than about 200 nm in diameter; and the exosome contains a guide RNA (gRNA) and a cytidine base editor, where the gRNA comprise a sequence that directs said n-Cas9-cytidine deaminase to edit the codon for amino acid 112 of the gene encoding ApoE4.

Abstract: The present disclosure relates to compounds which increase ?-oscillations in the brain. The disclosure further relates to methods of treating neurodegenerative diseases or disorders with the compounds disclosed herein.

Abstract: The present disclosure relates to compounds that are capable of inhibiting PRMT8 and/or upregulating SirT1. The disclosure further relates to methods of treating neurodegenerative diseases and disorders (e.g., Alzheimer's disease).

Abstract: The present disclosure relates to compounds that are capable of upregulating sAPP? and/or stabilizing reticulon-3. The disclosure further relates to methods of treating neurodegenerative diseases and disorders (e.g., Alzheimer's disease).

Abstract: The present disclosure relates to methods of treating coronavirus diseases comprising conjointly administering a combination of a PLpro inhibitor and an Mpro inhibitor, and to associated compositions.

Abstract: The present disclosure relates to compounds that increase sarcospan expression. The disclosure further relates to methods of treating a disease related to diminution or dysfunction of a dystrophin-related complex in a subject in need thereof.

Abstract: This invention provides improved synthetic exosomes for delivery a one or more therapeutic agents to the central nervous system. In certain embodiments the synthetic exosome comprises a liposome formed from a lipid bilayer, where said lipid bilayer comprises: one or more phospholipids selected from the group consisting of phosphate lipids, phosphoglycerol lipids, phosphocholine lipids, and phosphoethanolamine lipids where the lipid carbon chain ranges from 3 to 24 carbon atoms; cholesterol, a cholesterol derivative (e.g., cholesterol hemicsuccinate), or a phytosterol; and a non-ionic surfactant; wherein the lipid bilayer does not contain an alcohol; and the liposome ranges in size from about 50 nm up to about 200 nm in diameter. Typically, the synthetic exosome is capable of crossing the blood brain barrier without substantially leaking said therapeutic moiety.

Abstract: Provided herein are compounds of Formula I and their salts, and compositions thereof that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) and/or acetylcholinesterase (AChE) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Further disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).

Abstract: In certain embodiments allosteric inhibitors of BACE are provided. Illustrative inhibitors include but are not limited to various metformin analogs.

Abstract: Pharmaceutical compounds, compositions, methods, and uses therefor are presented using selected triazolopyridines and triazolopyrimidines to inhibit or reduce phosphorylation of tau proteins or that act as antagonists of corticotropin-releasing factor. Viewed from another perspective, compounds, compositions, and methods are presented for treating or preventing symptoms of Alzheimer's disease by inhibiting or reducing the phosphorylation of tau proteins.

Abstract: Compositions and methods of use for a compound having a chemical structure of Formula (I) and/or Formula (VII), or a pharmaceutically acceptable salt or solvate thereof, to increase muscle mass, muscle oxidative capacity, and muscle function and to treat muscular dystrophy, in particular limb girdle muscular dystrophy type 2A/R1/D1 are disclosed.

Abstract: In various embodiments, compositions and methods are provided for treatment and/or prevention of amyloidogenic diseases. In certain embodiments, the methods entail administering an effective amount of a tropinol ester to a subject in need thereof for prophylactic or therapeutic effect. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In certain embodiments, methods of reducing the risk, lessening the severity, or delaying the progression or onset of a disease characterized by beta-amyloid deposits in the brain of a mammal are also provided. In certain embodiments, methods of directly or indirectly inhibiting the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (AP-P664) in a mammal are provided.

Abstract: There are provided, inter alia, methods and compounds for activating a proliferative program in competent adult chondrocytes.

Abstract: Disclosed herein are compounds, compositions, and methods for treating neurodegenerative diseases, such as Alzheimer's disease.

Abstract: In various embodiments methods are provided for identifying and/or quantifying one or more antigens of interest (biomarkers) on the surface of cell- or tissue-specific exosomes.

Abstract: Pharmaceutical compounds, compositions, methods, and uses therefor are presented using selected triazolopyridines and triazolopyrimidines to inhibit or reduce phosphorylation of tau proteins or that act as antagonists of corticotropin-releasing factor. Viewed from another perspective, compounds, compositions, and methods are presented for treating or preventing symptoms of Alzheimer's disease by inhibiting or reducing the phosphorylation of tau proteins.

Abstract: Selected compounds, compositions, and methods for inhibiting BACE are presented that have relatively high selectivity towards APP via interaction of the inhibitor with both BACE and APP.

Abstract: In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.

Abstract: In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing or delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid prodrug (e.g., galangin prodrug).