Whitehead Institute for Biomedical Research

The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of Missouri

University of Pennsylvania

Nih Division of Extramural Inventions and Technology Resources (deitr)

Aaron D Gitler

Susan Lindquist

Anil Cashikar

Cole M Haynes

Antony A Cooper

Andrew Elden

Susan L Lindquist

Disclosed are compositions and methods for modulating expression of genes that function at the step of ER to Golgi trafficking. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Modulators of alpha-synuclein toxicity

Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.

Yeast cells expressing TAR DNA-binding protein 43 and uses therefor

Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Compositions and methods for diagnosis and treatment of ALS are provided.

Gene targets associated with amyotrophic lateral sclerosis and methods of use thereof

Compositions and methods are disclosed for identifying agents useful for the treatment of proteinopathies.

Methods of identifying modulators of TDP-43 mediated cellular toxicity

Disclosed are compositions and methods for modulating expression of genes that function at the step of ER of Golgi trafficking. Compounds that modulate expression of these genes of activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to threat of prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Growing community of inventors

Philadelphia, PA, United States of America

Aaron D Gitler