Abstract: Disclosed herein are compounds which inhibit PU.1, pharmaceutical formulations, and methods of treatment of PU.1-mediated diseases, such as Alzheimer's disease, inflammation, and diseases related to excessive myelin uptake.

Abstract: A method for increasing phase locking of neurons to gamma oscillations in at least one brain region of a subject for treating Alzheimer's disease in the subject in need thereof includes administering an inhibitor including a colony-stimulating factor-1 receptor (CSF1R) inhibitor or a colony-stimulating factor-1 (CSF1) inhibitor to the subject. The method also includes administering a stimulus to the subject having a frequency from about 20 Hz to about 60 Hz.

Abstract: A method of treating cognitive impairment associated with chemotherapy treatment in a subject in need thereof includes on-invasively delivering a combined stimulus to the subject to invoke gamma entrainment in a brain of the subject. The combined stimulus includes an auditory stimulus having a frequency of from about 20 Hz to about 60 Hz, and a visual stimulus having a frequency of from about 20 Hz to about 60 Hz.

Abstract: The present invention relates to polyhydroxylated benzophenone compounds useful in the treatment of neurodegenerative, neurological, psychiatric, and cognitive diseases, in particular those associated with a deficiency in HDAC1 deacetylase activity.

Abstract: The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R2a, R2b, R2c, R5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

Abstract: Provided herein are methods for obtaining populations of reprogrammed MO-homeostatic tolerogenic microglial cells. The methods include providing an initial population of monocytes, e.g., peripheral blood monocytes (PBMC), from a subject, and reprogramming the cells by maintaining the PBMC in culture ex vivo in the presence of a sufficient amount of transforming growth factor-beta (TGF?) and interferon-gamma (IFN?) for a time and under conditions sufficient for the cells to become M0-homeostatic tolerogenic microglia. Also provided are methods of use of these cells, e.g., for the treatment of neurodegenerative diseases associated with inflammation, e.g., Alzheimer's Disease (AD); Multiple Sclerosis (MS), e.g.

Abstract: The disclosure relates to compositions comprising PU.1 inhibitors as well as methods of making and using the same. In some embodiments, methods of screening compounds for PU.1 inhibition are disclosed. In some embodiments, methods of screening a plurality of compounds for PU.1 inhibition are disclosed. In some embodiments, lambda-beta binding (LBB) motifs are used to screen compounds for PU.1 inhibition. In some embodiments, methods of treating neurodegenerative disorders are disclosed. In some embodiments pharmaceutical compounds are provided. In some embodiments, methods of treating Alzheimer's disease, inflammation, or excessive myelin uptake with PU.1 inhibitors are disclosed.

Abstract: The present disclosure provides methods of inhibiting amyloid synthesis in a subject using small molecule inhibitors. The invention also includes methods of treating disease associated with amyloid synthesis, such as Alzheimer's disease. The small molecule inhibitors disclosed herein are compounds which are non-immunosuppressant cyclosporin including the pharmaceutically acceptable salts thereof.

Abstract: The present disclosure provides methods of inhibiting amyloid synthesis in a subject using cyclodextrin and analogs thereof. Small molecules (cyclodextrin) reverse APOE4-associated cholesterol phenotypes and lead to significantly improved myelination both human in vitro cultures and APOE4 targeted replacement mice. This demonstrates that APOE4 alters cholesterol synthesis and transport in oligodendrocytes which impairs myelination. Collectively, this work uncovers a pathogenic role of APOE4 in oligodendrocytes and myelination and enables therapeutic opportunities for Alzheimer's Disease.

Abstract: Devices, systems, and methods for a treating dementia or Alzheimer's disease in a subject in need thereof. In one example, combined auditory and visual stimuli having a frequency of about 20 Hz to about 60 Hz, and more specifically about 40 Hz, are non-invasively delivered to the subject to induce synchronized gamma oscillations in at least one brain region of the subject. In particular, pursuant to various treatment and exposure protocols, combined auditory and visual stimulation (as opposed to auditory or visual stimulation alone) promotes a microglia response in the medial prefrontal cortex (mPFC). More generally, combined auditory and visual stimulation induces an extended microglia clustering response in the auditory cortex, the visual cortex, and the mPFC.

Abstract: A method of treating neurodegeneration in a subject that includes administering a non-invasive tactile stimulus having a stimulus frequency of about 30 Hz to about 50 Hz to a subject to induce synchronized gamma oscillations in at least one portion of the peripheral nervous system of the subject, of the spinal cord of the subject, or both.

Abstract: The present disclosure provides, in some embodiments, in vitro brain (miBRAIN) having functional and structural properties of in vivo brain as well as methods of identifying compounds capable of influencing brain function.

Abstract: The present disclosure provides, in some embodiments, in vitro blood brain barrier (iBBB) having functional properties of in vivo BBB as well as methods of identifying compounds capable of traversing the iBBB. Compounds capable of crossing the iBBB and therapeutic uses of such compounds are also described.

Abstract: The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome.

Abstract: Devices, systems, and methods for treating dementia or Alzheimer's disease in a subject in need thereof. In one example, chronic visual stimuli having a frequency of about 30 Hz to about 50 Hz, and more specifically about 40 Hz, are non-invasively delivered to the subject to entrain gamma oscillations in multiple brain regions of the subject, including the prefrontal cortex (PFC) and the hippocampus. The entrained gamma oscillations modulate neuronal activity across multiple brain regions (e.g., facilitate functional binding of neural networks at low gamma frequencies) to induce various neuroprotective effects (e.g., amelioration of amyloid plaques and tau hyper-phosphorylation) and reduce neurodegeneration. Neuronal activity mediated by the chronic visual stimuli reduces an immune response in microglia and ameliorates aberrantly modified genes and proteins involved in membrane trafficking, intracellular transport, synaptic function, neuroinflammation and DNA damage response.

Abstract: Devices, systems, and methods for a treating dementia or Alzheimer's disease in a subject in need thereof. In one example, combined auditory and visual stimuli having a frequency of about 20 Hz to about 60 Hz, and more specifically about 40 Hz, are non-invasively delivered to the subject to induce synchronized gamma oscillations in at least one brain region of the subject. In particular, pursuant to various treatment and exposure protocols, combined auditory and visual stimulation (as opposed to auditory or visual stimulation alone) promotes a microglia response in the medial prefrontal cortex (mPFC). More generally, combined auditory and visual stimulation induces an extended microglia clustering response in the auditory cortex, the visual cortex, and the mPFC.

Abstract: The present invention relates to polyhydroxylated benzophenone compounds useful in the treatment of neurodegenerative, neurological, psychiatric, and cognitive diseases, in particular those associated with a deficiency in HDAC1 deacetylase activity.

Abstract: The invention relates to methods of using choline supplementation for treating APOE4-related disorders. In particular the methods are accomplished by administering choline treatment paradigms to re-establish lipid homeostasis in APOE4 carriers.

Abstract: The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome.

Abstract: The present invention relates to polyhydroxylated benzophenone compounds useful in the treatment of neurodegenerative, neurological, psychiatric, and cognitive diseases, in particular those associated with a deficiency in HDAC1 deacetylase activity.