Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons

Amelioration of Nicotine-Induced Conditioned Place Preference Behaviors in Mice by an FABP3 Inhibitor

“…Brain tissues were frozen in liquid nitrogen and preserved at −80 °C until analysis. Immunoblotting was performed as previously described [ 68 , 69 ]. In brief, proteins were extracted from the NAc and hippocampal CA1 regions using homogenizing buffer (50 mM Tris-HCl, pH 7.4, 0.5% Triton X-100, 4 mM EGTA, 10 mM EDTA, 40 mM Na 2 P 2 O 7 ·10H 2 O, 50 mM NaF, 1 mM Na 3 VO 4 , 1 mM dithiothreitol, 25 μg/mL pepstatin A, 50 μg/mL leupeptin, 50 μg/mL trypsin inhibitor, and 100 nM calyculin A).…”

Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins

“…In vitro experiments using neuro-2A cells showed that MF1 could reduce arachidonic acid-induced α-synuclein expression through targeting FABP3 and has potential applications in treating Parkinson’s disease. , A recent study also found that FABP3 could mediate nicotine-induced conditioned place preference behaviors in mice possibly through dopamine D2 receptor signaling and that MF1 could reduce nicotine-induced conditioned place preference behaviors. , Recently, these researchers synthesized a new compound called HY11-08 (HY08, compound 96 ) based on the MF1 backbone (Figure ). HY08 had a strong affinity for FABP3 ( K i = 24 nM) and a good affinity for FABP5 ( K i = 410 nM) and exhibited a neuroprotective effect for ischemic stroke in vivo possibly by targeting FABP3- and FABP5-induced mitochondrial damage . However, the structural basis for how these inhibitors interact with FABP3 was not elucidated.…”

“…MF6 (compound 111 ) exhibited an excellent affinity for FABP5 and FABP7 ( K d = 874 and 20 nM, respectively) and reduced symptoms of MOG 35–55 -administered autoimmune encephalomyelitis (mouse model for multiple sclerosis) and myelin loss during in vivo experiments through immune inhibition and oligodendrocyte protection and therefore could serve as a potential treatment for multiple sclerosis (Figure ). , HY08, a FABP3/FABP5 dual inhibitor based on the MF1 structure, demonstrates a potential neuroprotective effect in patients with ischemic stroke, as described above . However, only inhibitory activity and efficacy were tested for these compounds, and a detailed structural basis needs to be elucidated.…”

“…HY08 had a strong affinity for FABP3 (K i = 24 nM) and a good affinity for FABP5 (K i = 410 nM) and exhibited a neuroprotective effect for ischemic stroke in vivo possibly by targeting FABP3-and FABP5-induced mitochondrial damage. 122 However, the structural basis for how these inhibitors interact with FABP3 was not elucidated.…”

“…76,129 HY08, a FABP3/FABP5 dual inhibitor based on the MF1 structure, demonstrates a potential neuroprotective effect in patients with ischemic stroke, as described above. 122 However, only inhibitory activity and efficacy were tested for these compounds, and a detailed structural basis needs to be elucidated. Recently, Liang et al identified lycorine (compound 112) as an FABP5 inhibitor for treating acute myeloid leukemia (Figure 8).…”