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: The present disclosure relates to methods and compositions for elevating and stabilizing retromer for treating and/or preventing Alzheimer's disease and other neurodegenerative disorders. Additionally, the disclosure relates to adenoviral based therapy for treating Alzheimer's disease (AD), and other neurodegenerative conditions such as Parkinson's Disease (PD), neuronal ceroid lipofuscinosis (NCL), and transmissible spongiform encephalopathies (TSEs or prion disease), multiple system atrophy (MSA), Down's syndrome, and hereditary spastic paraplegia, 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), Lewy Body Disease (LBD), amyotrophic lateral sclerosis (ALS), frontal-temporal degeneration (FTD), ALS-FTD, and chronic traumatic encephalopathy (CTE).

Abstract: The present disclosure provides ICE-cleaved alpha-synuclein fragments as biomarkers for alpha-synuclein-associated disease or disorder and/or for ICE-regulator therapy.

Abstract: The present invention provides pharmaceutical compositions and related methods for stabilizing retromer in cells.

Abstract: Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

Abstract: The present disclosure provides ICE-cleaved alpha-synuclein fragments as biomarkers for alpha-synuclein-associated disease or disorder and/or for ICE-regulator therapy.

Abstract: The present disclosure identifies caspase-1/ICE as a therapeutic target for ?-synuclein associated diseases and disorders. Related methods and compositions are also provided.

Abstract: The present invention provides pharmaceutical compositions and related methods for stabilizing retromer in cells.

Abstract: One aspect of the invention relates to a method of treating or preventing a neurodegenerative disease, comprising the step of administering to a patient in need thereof a therapeutically effective amount of an inhibitor of the formation of advanced glycation end products. Another aspect of the invention relates to a proteasome activity-based screening assay to select compounds which may be useful for treating or preventing a neurodegenerative disease, and the materials used therein. Yet another aspect of the invention relates to molecules, and methods of use thereof, which bind at or adjacent to SOD-I Trp32, including molecules that bind in a site adjacent to SOD-I Trp32 whether or not it is oxidized, for treating or preventing neurodegenerative disease.

Abstract: The present disclosure provides ICE-cleaved alpha-synuclein fragments as biomarkers for alpha-synuclein-associated disease or disorder and/or for ICE-regulator therapy.

Abstract: The present invention provides the surprising finding that alpha-synuclein exists in vivo as a folded tetramer. Provided are various methods and technologies that arise from this finding, including methods and kits for identifying individuals susceptible to or suffering from certain diseases, disorders or conditions associated with stability of alpha-synuclein tetramers, and/or individuals likely (or not) to respond to therapy with agents that alter level and/or stability of alpha-synuclein tetramers.

Abstract: Disclosed herein are methods and related compositions for identifying compounds that stabilize natively folded tetrameric ?-synuclein. These methods and compositions are useful for the treatment and diagnosis of ?-synuclein-associated diseases and disorders.

Abstract: One aspect of the invention relates to a method of treating or preventing a neurodegenerative disease, comprising the step of administering to a patient in need thereof a therapeutically effective amount of an inhibitor of the formation of advanced glycation end products. Another aspect of the invention relates to a proteasome activity-based screening assay to select compounds which may be useful for treating or preventing a neurodegenerative disease, and the materials used therein. Yet another aspect of the invention relates to molecules, and methods of use thereof, which bind at or adjacent to SOD-I Trp32, including molecules that bind in a site adjacent to SOD-I Trp32 whether or not it is oxidized, for treating or preventing neurodegenerative disease.