Ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a therapeutic and diagnostic target in neurodegeneration, neurotrauma and neuro-injuries.

INTRODUCTION: Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease. In addition, certain post-translational modifications of UCH-L1 might promote the conversion of the cytosolic UCH-L1(C) to the membrane-associated UCH-L1(M) form, which seems to play a role in alpha-synucleinopathy formation. Thus, targeting the conversion of UCH-L1(C) to the UCH-L1(M) form might be the key to developing therapies for neurodegenerative diseases linked to UCH-L1. In parallel, UCH-L1 is also emerging as a promising neuron-derived biomarker for traumatic brain injury, ischemic and homographic stroke, pediatric hypoxic-ischemic encephalopathy, spinal cord injury, epileptic seizure and cardiac arrest. This shows that UCH-L1 has strong potential as a robust and universal biomarker target for various forms of CNS injury.