The present disclosure provides for characterization of normal flora and identifying biomarkers in the gut of healthy, neurotypical subjects. Aspect of the disclosure provide for the characterization of the gut microbiome in ADS subjects, characterized by reduced richness and significant loss of the ‘Prevotella-like enterotype’ compared to neurotypical subjects. The relative abundance of genera Prevotella, Coprococcus, Prevotellaceae and Veillonellaceae are significantly lower in autistic children than in neurotypical children. Further, Prevotella, is one of the three main classifiers for the human enterotypes, along with Bacteriodes and Ruminococcus. These three core genera are among main contributors in the principle component analysis. ‘Prevotella-like enterotype’ was absent in the autistic group, while neurotypical samples showed an even distribution among the three enterotypes. The present disclosure provides for an understanding the association between gut microbiota, health, and disease states, and provides for potential diagnostic and therapeutic targets.

The present invention relates to compositions and methods for promoting the degradation of misfolded proteins and protein aggregates. The compositions and methods may be used to treat a disorder associated with misfolded proteins or protein aggregates. In certain instances, the compositions and methods relate to modulators of one or more TRIM proteins or one or more STUbLs.

This invention provides a method for detecting cognitive disfunction diseases including mild cognitive impairment and Alzheimer's disease using a protein and a peptide of the protein different in the presence level in subjects having a normal cognitive function and patients suffering from cognitive disfunction diseases and a biomarker for detecting cognitive disfunction diseases including mild cognitive impairment and Alzheimer's disease containing the protein and the peptide. This invention is a biomarker for diagnosing cognitive disfunction diseases containing a prothrombin precursor protein of SEQ ID NO: 1 or a peptide THRB containing the amino acid sequence represented by SEQ ID NO: 2 which is a peptide of the protein, a diagnosis method for cognitive disfunction diseases using the biomarker, an antigen peptide represented by SEQ ID NO: 3 for creating a THRB peptide specific antibody to be used in the diagnosis method, and a cognitive disfunction disease diagnosis kit containing the THRB peptide specific antibody.

The present disclosure provides compounds of Formula (I) or (II), pharmaceutically acceptable salt, isotopic variant, stereoisomer, or a mixture thereof. Also provided are pharmaceutical compositions comprising a compound, methods of treating a poly(ADP-ribose)polymerase-1-mediated disease or disorder in a subject, methods of detecting a poly(ADP-ribose)polymerase-1-mediated neurodegenerative disease or disorder, or methods of monitoring cancer treatment in a subject. In some embodiments, the poly(ADP-ribose)polymerase-1-mediated disease or disorder is a neurodegenerative disease or cancer. ##STR00001##

Provided are aggregate alpha-synuclein specific antibodies as well as fragments, derivatives, and variants thereof as well as method related thereto for the early diagnostic and treatment of Parkinson's Disease and other Lewy body- and Lewy neurite-based diseases. Assays, kits, systems, and nanoparticle encapsulated compositions related to the antibodies or fragments, derivatives, and variants thereof are also disclosed.

Described is the use of GFAP as a marker of drug-induced cellular toxicity and depression.

A composition having one or more nanoneedles is provided, where each nanoneedle has a silver tip and one or more of the silver tips comprise an AgCl layer. In one approach, one or more of the silver tips further include a layer of thiol-polyethylene glycol. A method of resistive pulse detection involving a protein pore is also provided. The method involves reconstituting one or more protein pores in a lipid membrane formed on the tip of a nanoneedle, then applying a potential across the membrane and detecting resistive pulses.

A method of treating a synucleinopathy with a peptide (C)DQPVLPD (SEQ ID NO: 59), (C)DMPVLPD (SEQ ID NO: 60), (C)DSPVLPD (SEQ ID NO: 61), (C)DQPVLPDN (SEQ ID NO: 64), (C)DMPVLPDN (SEQ ID NO: 65), (C)DSPVLPDN (SEQ ID NO: 66), (C)HDRPVTPD (SEQ ID NO: 70), (C)DRPVTPD (SEQ ID NO: 71), (C)DVPVLPD (SEQ ID NO: 72), (C)DTPVYPD (SEQ ID NO: 73), (C)DTPVIPD (SEQ ID NO: 74), (C)HDRPVTPDN (SEQ ID NO: 75), (C)DRPVTPDN (SEQ ID NO: 76), (C)DVPVLPDN (SEQ ID NO: 78), (C)DTPVYPDN (SEQ ID NO: 79), (C)DQPVLPDG (SEQ ID NO: 81), (C)DMPVLPDG (SEQ ID NO: 82), (C)DSPVLPDG (SEQ ID NO: 83), (C)DHPVHPDS (SEQ ID NO: 86), (C)DMPVSPDR (SEQ ID NO: 87), (C)DRPVYPDI (SEQ ID NO: 90), (C)DHPVTPDR (SEQ ID NO: 91), (C)DTPVLPDS (SEQ ID NO: 93), (C)DMPVTPDT (SEQ ID NO: 94), (C)DAPVTPDT (SEQ ID NO: 95), (C)DSPVVPDN (SEQ ID NO: 96), (C)DLPVTPDR (SEQ ID NO: 97), (C)DSPVHPDT (SEQ ID NO: 98), (C)DAPVRPDS (SEQ ID NO: 99), (C)DMPVWPDG (SEQ ID NO: 100), (C)DRPVQPDR (SEQ ID NO: 102), (C)YDRPVQPDR (SEQ ID NO: 103), (C)DMPVDADN (SEQ ID NO: 105), DQPVLPD(C) (SEQ ID NO: 106), and DMPVLPD(C) (SEQ ID NO: 107.

The subject matter disclosed herein relates to methods of identifying pharmacophores and inhibitors against protein aggregation. The present disclosure also provides pharmacophores themselves and medical uses of agents in the treatment of diseases associated with protein aggregation.

The invention relates to methods for determining whether a subject is afflicted with a motor neuron disease, the method comprising conducting an analysis of cerebrospinal fluid and/or plasma, measuring the level of one or more sterol/oxysterol analytes, and comparing these to reference values. Further, the invention relates to methods of identifying agents suitable for the treatment of MND, and monitoring the progress of the disease.