DnaJC5γ Inhibitors

The DnaJC5γ inhibitors primarily function by inhibiting key processes and pathways that DnaJC5γ is involved in. Cyclosporin A and FK506 are inhibitors of calcineurin, a protein that dephosphorylates synapsins. DnaJC5γ is involved in synaptic vesicle exocytosis, which is mediated by synapsins. Therefore, inhibition of calcineurin can indirectly decrease the functional activity of DnaJC5γ. Similarly, Guanabenz inhibits the stress-induced phosphatase PP1/GADD34 complex, which can impact the phosphorylation status of synapsins, indirectly leading to the decreased functional activity of DnaJC5γ. Leflunomide, an inhibitor of dihydroorotate dehydrogenase, indirectly affects DnaJC5γ by inhibiting nucleotide synthesis, which is required for synaptic vesicle exocytosis.

Bafilomycin A1 and Concanamycin A function by inhibiting the vacuolar type H+-ATPase (V-ATPase), a crucial component for the acidification of vesicles, an essential step for neurotransmitter loading and hence synaptic vesicle exocytosis. Inhibition of this process can indirectly decrease the functional activity of DnaJC5γ. Salubrinal, an inhibitor of eIF2α dephosphorylation, can affect protein synthesis, which indirectly impacts the functional activity of DnaJC5γ, as it is involved in synaptic vesicle exocytosis. Tunicamycin inhibits N-linked glycosylation, a post-translational modification that can indirectly affect the functional activity of DnaJC5γ, which assists in protein folding and maturation. Proteasome inhibitors like MG132 and Bortezomib can indirectly affect the functionality of DnaJC5γ, which might be involved in protein degradation pathways. Finally, 2-Deoxyglucose and 3-Bromopyruvate, inhibitors of glycolysis, can indirectly affect the functional activity of DnaJC5γ, which is part of protein homeostasis requiring energy.