In multiple system atrophy (MSA) patients, alpha-synuclein (ɑSyn) predominantly accumulates in oligodendrocytes and forms glial cytoplasmic inclusions (GCIs). Such changes induce oligodendrocyte degeneration and demyelination, and damages trophic support of glial cells to neurons. The toxic formations of aSyn oligomers or fibrils in glial cells are triggered by cellular oxidative stress. Exposure to polyunsaturated fatty acids such as arachidonic acid (AA) increases reactive oxygen species (ROS) in neurons. Fatty acid-binding proteins (FABPs), a family of transporter proteins, bind with high affinity to long-chain fatty acid such as AA. FABP7 is primarily expressed in the oligodendrocytes and neural stem cells. To elucidate FABP7‘s involvement in MSA, we overexpressed ɑSyn in U251 human glioblastoma cells and confirmed FABP7 toxicity via its enhancement of ɑSyn oligomer formation. FABP7-induced ɑSyn aggregation significantly increased by exposure to AA in U251 cells. FABP7-induced ɑSyn oligomerization was associated with cell death in U251 cells. FABP7-induced ɑSyn oligomerization was also evidenced in both KG-1C human oligodendroglial cells and oligodendrocyte precursor cells (OPCs). FABP7 ligand 6 (BRI-601) disrupted the FABP7–ɑSyn interaction in these glial cells. Psychosine treatment also triggered ɑSyn oligomerization by FABP7 through phospholipase A2 activation, and induced KG-1C and OPCs cell death. BRI-601 also rescued the psychosine toxicity in glial cells. Taken together, FABP7 triggers aSyn oligomerization associated with oxidative stress, while BRI-601 can prevent the oxidative stress-induced ɑSyn toxicities, thereby rescuing MSA progression.