Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a disorder, such as schizophrenia or bipolar disorder, by increasing or decreasing proline levels. Further provided are methods of predicting and monitoring the clinical response in a patient, and diagnostic systems for identifying a patient likely to benefit from proline modulation.

Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

Abstract: Biomarkers for assessing the efficacy of prophylactic treatments of stress-induced affective disorders are provided.

Abstract: Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and/or enhancing stress resilience in a subject. In certain embodiments, an effective amount of (R,S)-ketamine or (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) is administered to a female or male subject prior to a stressor.

Abstract: The present disclosure relates to methods and compositions which prevent and protect against all three types of stress-induced maladaptive behaviors- fear, depressive-like, and anxiety-like behavior, which in turn can prevent a wide variety of stress-induced fear, anxiety, and depressive disorders. In some aspects, the compositions and methods use a serotonin 4 receptor (5-hydroxytryptamine (serotonin) receptor 4, or 5-HT4R) agonist in combination with: ketamine, a ketamine analog, or a pharmaceutically acceptable salt, derivative, or metabolite thereof; an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor (NMDAR); or an agonist of the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). In certain aspects, the present composition or compositions can be administered prior to a stressor. In certain aspects, the present composition or compositions can be administered after a stressor.

Abstract: Biomarkers for assessing the efficacy of prophylactic treatments of stress-induced affective disorders are provided.

Abstract: The present disclosure relates to methods and compositions for elevating and stabilizing retromer for treating and/or preventing Alzheimer's disease and other neurodegenerative diseases or disorders. Additionally, the disclosure relates to gene therapy combined with a pharmacological retromer chaperone therapy for treating and/or preventing Alzheimer's disease (AD), and other neurodegenerative diseases or disorders such as Parkinson's Disease (PD), amyotrophic lateral sclerosis (ALS), neuronal ceroid lipofuscinosis (NCL), and transmissible spongiform encephalopathies (TSEs or prion disease), multiple system atrophy (MSA), as well as tauopathies such as progressive supranuclear palsy (PSP), frontotemporal lobar dementia linked to chromosome 17q21-22 and its subtypes (FTLD-17/FTLD-Tau), and chronic traumatic encephalopathy (CTE).

Abstract: Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and/or enhancing stress resilience in a subject. In certain embodiments, an effective amount of (R,S)-ketamine or (2R, 6R)-hydroxynorketamine ((2R, 6R)-HNK) is administered to a female or male subject prior to a stressor.

Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and methods of using the compound to treat pain, depressive disorders, mood disorders, anxiety disorders, opioid use disorder, and opioid withdrawal symptoms.

Abstract: Methods for prophylactically treating or treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. In certain embodiments, an effective amount of an antagonist of the N-methyl-D-aspartate (NMDA) receptor, such as fluoroethylnormemantine, or a pharmaceutically acceptable salt or derivative thereof, is administered to a subject prior to, during, and/or after, a stressor.

Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a disorder, such as schizophrenia or bipolar disorder, by increasing or decreasing proline levels. Further provided are methods of predicting and monitoring the clinical response in a patient, and diagnostic systems for identifying a patient likely to benefit from proline modulation.

Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

Abstract: The present invention provides methods for assessing whether a subject is at risk of developing a neurological disorder, diagnosing or confirming whether a subject is afflicted with a neurological disorder, assessing a neurological disorder is developing in a subject who has been identified as being at risk of developing the neurological disorder, assessing whether a subject afflicted with a neurological disorder is likely to benefit iron a therapy, assessing whether a subject afflicted with a neurological disorder has benefited from a therapy, treating a subject afflicted with a neurological disorder, and prophylactically treating a subject who has been identified as being at risk, of developing a neurological disorder. The present invention also provides epitopes, compounds and compositions relating to these methods.

Abstract: The treatment of age-related macular degeneration with the chronic administration of the neurotrophic peptidergic compound P021. Chronic treatment of animal models for age-related macular degeneration prevented the pathological changes associated with age-related macular degeneration, including photoreceptor degeneration, lipofuscin granules, vacuoles and atrophy in retinal pigment epithelium (RPE), Bruch's membrane (BM) thickening, rosette-like structure formation, microgliosis and astrogliosis.

Abstract: The treatment of abnormal hyperphosphorylation of tau in brains of patients with metabotropic glutamate receptor 5 (mGluR5) antagonists. The treatment uses the signaling pathway in which the inhibition of protein phosphatase 2A (PP2A) through phosphorylation of its catalytic subunit PP2Ac at Tyr307 is induced by the activation of metabotropic glutamate receptor 5 (mGluR5) and leads to hyperphosphorylation of tau. The mGluR5-PP2A axis has a central role in neurofibrillary degeneration and thus is be a therapeutic target for the treatment of tauopathies.

Abstract: A method of treating tau pathologies, such as Alzheimer's disease, involving the administration of antibodies specific to the amino terminal region of human tau (amino acid residues 6-18 or 184-195) to provide passive immunization. The administration of such antibodies can reduce total tau levels, decrease tau hyperphosphorylation, and improve reference memory. Passive immunization with antibodies targeting the N-terminal projection domain of tau reduces both total and hyperphosphorylated tau was found effective in aged 3×Tg-AD mice, a generally accepted mouse model of Alzheimer's disease and frontotemporal dementia in humans.

Abstract: An assay for a GCH1 allele and associated genotype for the screening, prediction, diagnosis, prognosis, treatment and treatment response of psychiatric, neuropsychiatric, and neurological disorders, such as schizophrenia, schizoaffective disorder and bipolar disorder, and for defining treatments of such disorders. The presence of a variant in the GCH1 gene, alone or in conjunction with a measurement of low or altered biopterin, or altered BH4 system measures, is used to screen or diagnose subjects at risk for developing a psychiatric, neuropsychiatric, or neurological disorder. The genetic assay, with or without a biopterin or BH4 system assay, may also be used to determine treatment regimens. For subjects with an impaired BH4 system, treatments to increase or normalize biopterin, BH4, or the BH4 system can also be used, such as BH4 supplementation, lithium treatment, phenylalanine treatment, or other treatments and therapies.

Abstract: An assay for a GCH1 allele and associated genotype for the screening, prediction, diagnosis, prognosis, treatment and treatment response of psychiatric, neuropsychiatric, and neurological disorders, such as schizophrenia, schizoaffective disorder and bipolar disorder, and for defining treatments of such disorders. The presence of a variant in the GCH1 gene, alone or in conjunction with a measurement of low or altered biopterin, or altered BH4 system measures, is used to screen or diagnose subjects at risk for developing a psychiatric, neuropsychiatric, or neurological disorder. The genetic assay, with or without a biopterin or BH4 system assay, may also be used to determine treatment regimens. For subjects with an impaired BH4 system, treatments to increase or normalize biopterin, BH4, or the BH4 system can also be used, such as BH4 supplementation, lithium treatment, phenylalanine treatment, or other treatments and therapies.

Abstract: Five tetra peptides corresponding to different active regions of brain derived neurotrophic factor (BDNF) that are neurotrophic and can modulate BDNF signaling in a partial agonist/antagonist way. The peptides offer a therapeutic approach to neural pathologies where BDNF levels are dysregulated.

Abstract: An assay for a GCH1 allele and associated genotype for the screening, prediction, diagnosis, prognosis, treatment and treatment response of psychiatric, neuropsychiatric, and neurological disorders, such as schizophrenia, schizoaffective disorder and bipolar disorder, and for defining treatments of such disorders. The presence of a variant in the GCH1 gene, alone or in conjunction with a measurement of low or altered biopterin, or altered BH4 system measures, is used to screen or diagnose subjects at risk for developing a psychiatric, neuropsychiatric, or neurological disorder. The genetic assay, with or without a biopterin or BH4 system assay, may also be used to determine treatment regimens. For subjects with an impaired BH4 system, treatments to increase or normalize biopterin, BH4, or the BH4 system can also be used, such as BH4 supplementation, lithium treatment, phenylalanine treatment, or other treatments and therapies.