Table 2 Overview of ALOX-associated LM and their functions in MS pathogenesis

Leukotrienes

Leukotriene B₄ (LTB₄)

ALOX5/FLAP complex + 

LTA₄ hydrolase

BLT1

• Chemo-attractant for Th17 lymphocytes in vitro

[108, 110]

BLT2

• Unknown

–

PPAR-α

• Induces macrophage apoptosis in vitro

[115, 116]

CysLTR1

• Chemo-attractant for Th17 lymphocytes

[111]

Leukotriene D₄ (LTD₄)

ALOX5/FLAP complex + 

LTC₄ hydrolase + 

Y-glutamyl transferase

CysLTR1/2

• Chemo-attractant for Th17 lymphocytes

[111, 121, 122]

Leukotriene E₄ (LTE₄)

ALOX5/FLAP complex + 

LTC₄ hydrolase + 

Y-glutamyl transferase + 

LTD₄ dipeptidase 1/2

CysLTR1/2

–

–

HETEs

5-HETE

ALOX5/FLAP complex

OXER1

• Promote the migration of monocytes

[124,125,126]

5-KETE

ALOX5/FLAP complex + 

5-HEDH

OXER1

• Promote the migration of monocytes

[124,125,126]

11-HETE

Non-enzymatic/

Cytochrome P450/

COX-1/2/

Non-enzymatic

–

• Associates with lipid peroxidation

[125,126,127]

12-HETE

ALOX-12

GPR31

• Promote chemotaxis of leukocytes

• Induce oxidative stress via an ERK1/2-ALOX-12-ROS pathway

• May promote apoptosis signaling of mature OLs

120

BLT-2

• Promote chemotaxis of leukocytes

• Induce oxidative stress via an ERK1/2-ALOX-12-ROS pathway

[134,135,136,137]

15-HETE

ALOX15-1/

ALOX15-B

BLT-2

• Induce foam cell formation

[112, 146, 148,149,150, 152,153,154]

PPAR-y

• Inhibits LTB4-induced chemotaxis of PMN leukocytes in vitro

• Promote a pro-resolving phenotype in microglia/macrophages

[146,147,148,149,150, 152,153,154,155]