Delving into the Latest Updates on NAV-2729 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

ARF6

Mechanism

ARF6 modulators(ADP ribosylation factor 6 modulators)

Therapeutic Areas

Infectious DiseasesRespiratory DiseasesOther Diseases

Active Indication

InflammationCOVID-19

Inactive Indication-

Originator Organization

Navigen, Inc.Startup

Active Organization

Rowan University

Sygnature Discovery Ltd.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractSchwann cells are glial cells in the peripheral nervous system (PNS); they wrap neuronal axons with their differentiated plasma membranes called myelin sheaths. Although the physiological functions, such as generating saltatory conduction, have been well studied in the PNS, the molecular mechanisms by which Schwann cells undergo their differentiation program without apparent morphological changes before dynamic myelin sheath formation remain unclear. Here, for the first time, we report that Arf6, a small GTP/GDP-binding protein controlling morphological differentiation, and the guanine-nucleotide exchange factors cytohesin proteins are involved in the regulation of Schwann cell differentiation marker expression in primary Schwann cells. Specific inhibition of Arf6 and cytohesins by NAV-2729 and SecinH3, respectively, decreased expression of marker proteins 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and glial fibrillary acidic protein (GFAP). Similar results using promoter assays were observed using the IMS32 Schwann cell line. Furthermore, using an affinity-precipitation technique, we identified Bcl2-like 12 (Bcl2l12) as a novel GTP-bound Arf6-interacting protein. Knockdown of Bcl2l12 using a specific artificial miRNA decreased expression of marker proteins. The knockdown also led to decreased filamentous actin extents. These results suggest that Arf6 and Bcl2l12 can trigger Schwann cell differentiation, providing evidence for a molecular relay that underlies how Schwann cells differentiate.

100 Deals associated with NAV-2729

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