Vib Vzw

Katholieke Universiteit Leuven, Ku Leuven R&d

Vrije Universiteit Brussel

Katholieke Universiteit Leuven

Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw

Bart De Strooper

Serge Muyldermans

Joost Schymkowitz

Frederic Rousseau

Lujia Zhou

Wim Annaert

Els Marjaux

Patrik Verstreken

Vanessa Morais Epifânio

Lucia Chávez Gutiérrez

Maria Szaruga

Joris De Wit

Ragna Sannerud

Katrijn Coen

Heather Rice

Amantha Thathiah

Ivo Da Rocha Martins

The present invention relates to the field of neurodegenerative diseases. More specifically, the present invention relates to a screening assay to produce compounds stabilizing the gamma-secretase enzyme substrate complex, thereby increasing gamma-secretase processivity while attenuating the release of longer A&#x3b2; peptides. More specifically, gamma-secretase stabilizing compounds increase thermostability of the enzyme/substrate complexes acting in the sequential &#x3b3;-secretase processing of APP, to result in reduced amyloidogenic A&#x3b2; production, thereby preventing Alzheimer disease.

&#x393;-secretase stabilizing compound screening assay

The present invention relates to the field of disorders of the central nervous system, in particular neurological and psychiatric disorders, and the prevention and/or treatment thereof. In particular, the present invention relates to the finding that soluble amyloid precursor protein a (sAPP&#x3b1;) presents a particular binding site, which allows for binding to the GABAR1a receptor, thereby causing an agonistic effect through specific binding to Sushi domain 1 of GABAR1a. As a result, the frequencies of excitatory and inhibitory postsynaptic currents are reduced. Accordingly, the invention provides compounds able to interfere with the association of sAPP&#x3b1; with Sushi domain 1 of GABAR1a and as such with selective impairment of GABAR1sa beneficial in neurological and psychiatric disorders. The invention as well provides methods and (high content) screening assays for the production of said compounds.

Therapeutic agents for neurological and psychiatric disorders

Described are single domain antibodies with a specificity for BACE1. More specifically, described are single variable-domain antibodies derived from camelids that bind to BACE1 and are capable of inhibiting the activity of BACE1. The antibodies can be used for research and medical applications. Specific applications include the use of BACE1-specific antibodies for the treatment of Alzheimer's disease.

Single domain antibodies capable of modulating BACE activity

The present application relates to the field of Parkinson's disease (PD), particularly sporadic PD or PD associated with mutations in the mitochondrial kinase PINK1. A new substrate for this kinase, NdufA10, is identified herein. In Parkinson's disease, this protein is dephosphorylated, which is linked to a loss of mitochondrial membrane potential. It is shown that restoring or mimicking phosphorylation of NdufA10 restores the phenotypic defects associated with Parkinson's disease and is thus a new therapeutic paradigm.

Restoring phosphorylation of a novel PINK1 substrate to treat parkinson's disease

The present invention relates to antibodies with a specificity for BACE1. More specifically, the invention provides monoclonal antibodies that bind to BACE1 and are capable of inhibiting the activity of BACE1 and methods producing these antibodies. The antibodies can be used for research and medical applications. Specific applications include the use of BACE1-specific antibodies for the treatment of Alzheimer's disease.

BACE1 inhibitory antibodies

The invention relates to the field of disorders of the peripheral or central nervous system, in particular, Alzheimer's disease, and the prevention and/or treatment thereof. In particular, the invention relates to ARF6 and/or ARF6 effector proteins as new targets in Alzheimer's disease, and based thereon, screening methods for compounds that reduce amyloid beta peptide formation in mammalian cells by affecting ARF6-mediated endosomal sorting.

Screening methods for compounds that modulate ARF-6 mediated endosomal redistribution

The invention relates to the field of disorders of the peripheral or central nervous system, in particular, Alzheimer's disease, and the prevention and/or treatment thereof. In particular, the invention relates to the screening of compounds that modulate GPR3 activity and/or beta-arrestin signaling in a mammalian cell and, in particular, compounds that reduce the formation of amyloid beta peptides. The invention also relates to inhibiting agents targeting beta-arrestin signaling and pharmaceutical compositions thereof, and their use in therapeutic applications of those disorders.

Screening for compounds that modulate GPR3-mediated beta-arrestin signaling and amyloid beta peptide generation

The present invention relates to the identification of the molecular binding domains between presenilins and its substrates such as amyloid precursor protein and telencephalin. These binding domains can be efficiently used in drug screening assays to screen for compounds capable of modulating the interaction between presenilins and type I transmembrane proteins. The invention further relates to compounds capable of modulating the interaction.

Growing community of inventors

Leuven, Belgium

Bart De Strooper