ALZHEIMER'S DISEASE & TAUOPATHY

NEUROBIOLOGY

Fluofarma's contract research services in neuroscience focus on central nervous system (CNS) disorders. We offer to validate drug targets and test neuroactive compounds through customized cell-based assays & quantitative biomarker analysis in brain tissues. Our cell-to-tissue approach delivers solid preclinical proof-of- concepts for CNS drug development.

ALZHEIMER'S DISEASE & TAUOPATHY

Hyper-phosphorylation of Tau and aberrant gamma-secretase activity are respectively involved in the formation of intracellular neurofibrillary tangles and in the extracellular deposition of amyloid plaques in the brain – the two hallmarks of Alzheimers’s disease. Two in vitro pharmacological cell models are available at Fluofarma to identify or characterize compounds targeting Tau phosphorylation cascade or γ-secretase activity.

OKADAIC ACID-INDUCED TAU HYPER-PHOSPHORYLATION ASSAY

Okadaic acid-induced Tau-hyperphosphorylation (red) in a primary rat cortex culture. Nuclei are in blue.

Okadaic acid-induced Tau-hyperphosphorylation (red) in a primary rat cortex culture. Nuclei are in blue.

Fluofarma developed an in vitro cellular model of tauopathy to identify and characterize compounds preventing Tau hyper-phosphorylation:

> A well-characterized and predictive pharmacological model of Tauopathy: primary rat cortical cultures are treated with okadaic acid in microplates

> A straightforward readout: phospho-Tau is quantified at the single-cell level using immunofluorescence & high-content imaging

GAMMA-SECRETASE ACTIVITY WITH RECOMBINANT BIOSENSOR IN HETEROLOGOUS CELL CLONE

Fluofarma developed a proprietary biosensor based on a GFP-like reporter linked to C99 protein (beta-amyloid precursor), which is specifically cleaved by gamma-secretase. The resulting assay, optimized for high-throughput screening, is particularly suited for the selection of gamma-secretase inhibitors:

> Cost-efficientreagentless quantification of γ-secretase activity by flow cytometry

> High-throughput: stably expressed in human cell clones cultured in microplate format

> Robust: our gamma-secretase assay was cross-validated by immunocytochemistry.