Johns Hopkins University

Gpi Nil Holdings Inc.

Valted, LLC

Other

The United States of America

Southern Methodist University

Sungkyunkwan University

Ted M Dawson

Solomon H Snyder

Valina L Dawson

Joseph P Steiner

Gregory S Hamilton

Han Seok Ko

Jooho Shin

Seulki Lee

Magdalena Scully

Seung Pil Yun

W Ernest Lyons

Edwin B George

Edward R Biehl

Sukanta Kamila

George R Uhl

Edythe D London

David S Bredt

Jie Zhang

Richard J Traystman

Patricia D Hurn

Kenji Sampei

Shaida A Andrabi

Allen S Mandir

Jun Bao

Ho Chul Kang

Mikael J Eliasson

Andrew Pieper

Areum Jo

Tae-In Kam

Liana Rosenthal

Shaida Andrabi

Yunjong Lee

Joo-ho Shin

Poly(ADP-ribose) (PAR) is a protein implicated in numerous neurodegenerative disease states including Parkinson's disease (PD). To date, no routine laboratory test has been developed to diagnosis, assess or monitor patients suffering from PD. Disclosed herein a novel method to assess the PAR concentration in the cerebral spinal fluid (CSF) of a patient and correlate that concentration to the medical condition of a patient with PD. Also disclosed is the use of PAR as a biomarker for PD.

Detection of PAR in the CSF of patients with Parkinson's disease

The present invention relates to compositions and methods for treating neurodegenerative conditions using GLP-1r agonists. In certain embodiments, long-acting GLP-1r agonists have neuroprotective and disease modifying effects on the central nervous system.

Long-acting GLP-1r agonist as a therapy of neurological and neurodegenerative conditions

Long-acting GLP-1R agonist as a therapy of neurological and neurodegenerative conditions

Research into neuroprotective mechanisms has at its heart the goal of developing new therapeutic strategies to treat patients. For example, the compositions and induction strategies disclosed herein have use for acute injuries such as stroke or trauma, and would be extremely useful in treating patients undergoing cardiac bypass surgery, neurosurgery or other surgical cohorts where ischemia is a risk. Further, patients with subarachnoid hemorrhage, transient ischemic attacks, soldiers at risk for blast injury or patients suffering from chronic neurodegenerative diseases would also benefit from enhanced neuronal survival based upon the techniques and compositions disclosed herein. In addition, protecting against cell death by, for example, interfering with PAR polymer signaling via the compositions and processes disclosed herein, offers new therapeutic strategies for the treatment of neurologic disorders.

Treatment and prevention of pathological conditions using iduna related techniques and compositions

The present invention provides methods of making and using 5-(2-(indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one derivatives having HIV-1 or JSP-1 inhibitory activity.

Methods of making and using thioxothiazolidine and rhodanine derivatives as HIV-1 and JSP-1 inhibitors

Parkinson's disease is caused by the preferential loss of substantia nigra dopamine neurons. A Parkin Interacting Substrate, PARIS (ZNF746) is identified. The levels of PARIS are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin. PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human brain Parkinson's disease patients. PARIS represses the expression of the transcriptional co-activator, PGC-1&#x3b1; and the PGC-1&#x3b1; target gene, NRF-1 by binding to insulin response sequences in the PGC-1&#x3b1; promoter. Conditional knockout of parkin in adult animals leads to progressive loss of dopamine (DA) neurons that is PARIS dependent. Overexpression of PARIS causes selective loss of DA neurons in the substantia nigra, which is reversed by either parkin or PGC-1&#x3b1; co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Transcriptional repression leading to parkinson's disease

Transcriptional repression leading to Parkinson's disease

This invention relates to the method of using neurotrophic pipecolic acid derivative compounds having an affinity for FKBP-type immunophilins as inhibitors of the enzyme activity associated with immunophilin proteins, and particularly inhibitors of peptidyl-prolyl isomerase or rotamase enzyme activity to stimulate or promote neuronal growth or regeneration.

Inhibitors of rotamase enzyme activity

Immunophilin-binding agents inhibit the phosphatase calcineurin, leading to the increased phosphorylation of certain brain proteins, including nitric oxide synthase. The increased levels of phosphorylation of nitric oxide synthase inhibits the enzymatic production of nitric oxide. Thus the neurotoxic effects of glutamate, which are ordinarily the result of vascular strokes and other neurodegenerative diseases, are minimized, because the neurotoxic effects are at least partially mediated by nitric oxide. Thus immunophilin-binding drugs can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease.

Immunophilin-binding agents prevent glutamate neurotoxicity associated with vascular stroke and neurodegenerative diseases

Neutral tissue damage resulting for ischemia and reperfusion injury or neurodegenerative diseases can be prevented by administering therapeutically effective amounts of certain selective inhibitors of poly(ADP-ribose)polymerase. The inhibitors can be administered intravenously, intraperitoneally, intramuscularly, intraventricularly, or orally. They can be administered as a capsule or tablet containing single or divided dose. Alternatively, the inhibitors can be administered as a sterile solution, suspension or emulsion.

Method of using selective parp inhibitors to prevent or treat neurotoxicity

Immunophilin ligands act by binding to receptor proteins, immunophilins, which in turn can bind to and regulate the Ca.sup.2+ dependent phosphatase, calcineurin, and the Ca.sup.2+ release channel, the ryanodine receptor. Immunophilin ligands have been discovered to enhance neurite outgrowth in neuronal cell systems by increasing sensitivity to neurotrophic factors. The effects of the immunophilin ligands are detected at subnanomolar concentrations indicating therapeutic application in diseases involving neural degeneration.

Stimulating nerve growth with immunophilins

Direct influences on nerve growth of agents that interact with

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Baltimore, MD, United States of America

Ted M Dawson