TARGETING LSD1 TO PROMOTE FUNCTIONAL RECOVERY AFTER NEURAL TRAUMA

TRAUMATIC INJURIES OF THE NERVOUS SYSTEM ARE A LEADING CAUSE OF NEUROLOGIC MORBIDITY AND MORTALITY WORLDWIDE. AT THE MOMENT, THERE ARE NO CURRENT AVAILABLE TREATMENTS THAT YIELD SIGNIFICANT FUNCTIONAL RESTORATION AFTER THIS TYPE OF INJURIES. FOR THIS PURPOSE, SPECIFIC EMPHASIS IS NEEDED TO FIND A PRECISE THERAPEUTIC INTERVENTION TO PROMOTE ACUTE NEUROPROTECTION, AND TO BOOST INTRINSIC NEUROPLASTICITY. WE HAVE OBSERVED THAT LYSINE SPECIFIC DEMETHYLASE 1A (LSD1) INHIBITION ENHANCES THE FUNCTIONAL OUTCOME AFTER A TRAUMATIC INJURY OF THE CENTRAL AND OF THE PERIPHERAL NERVOUS SYSTEM. HOWEVER, THE MOLECULAR EVENTS UNDERLYING THESE MECHANISMS, ARE NOT KNOWN. THUS, TO PURSUE WITH POTENTIAL CLINICAL APPLICATIONS OF LSD1 INHIBITION, WITH THIS PROJECT, WE AIM TO FIND THE CELLULAR AND MOLECULAR MECHANISMS BY WHICH LSD1 INHIBITION PROMOTES ENHANCED NEUROPROTECTION AND FUNCTIONAL OUTCOME AFTER SPINAL CORD INJURY. THEN, WE PRETEND TO DEVELOP NOVEL EPIGENETIC THERAPEUTIC TOOLS BY SPECIFIC TARGETING OF PRECISE PATHWAYS MODIFIED BY LSD1 INHIBITION, WHICH WOULD NARROW POTENTIAL UNDESIRABLE EFFECTS OF GLOBAL LSD1 PHARMACOLOGICAL INHIBITION. FURTHER, SINCE BRAIN STROKE SHARES MANY PATHOPHYSIOLOGICAL EVENTS WITH SPINAL CORD INJURY, WE AIM TO PROVIDE WITH A NOVEL APPLICATION OF LSD1 INHIBITION FOR BRAIN STROKE RECOVERY. EFFECTS OF LSD1 MODULATION ON NEUROPROTECTION AND NEUROPLASTICITY AFTER BRAIN STROKE WILL BE DECIPHERED. THUS, THE RESULTS FROM THIS PROJECT MAY BE VALUABLE FOR THERAPEUTIC INNOVATION. IN ADDITION, THE PRESENT PROJECT WILL OPEN A THERAPEUTIC WINDOW FOR OTHER HUMAN NEURODEGENERATIVE DISEASES THAT REQUIRE NERVOUS SYSTEM NEUROPROTECTION AND/OR NEUROREGENERATION IN THE NEAR FUTURE.