Role of Neddylation in Neurodegenerative Diseases

Neurodegenerative diseases are characterized by progressive loss of neurons in specific regions of the brain. Neuronal death is often associated with the accumulation of misfolded proteins due to genetic mutations or abnormal protein homeostasis. An essential mechanism for regulating the clearance of misfolded proteins is neddylation, a post-translational modification closely related to ubiquitination. Neddylation is brought about by conjugating neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to target substrates through a cascade of cellular events. Neddylation is crucial for many biological processes, and dysfunctional neddylation is implicated in several neurodegenerative diseases. This review discusses the current understanding of the role of neddylation pathways in neurodegenerative disorders and the emergence of neddylation signaling as a potential target for drug discovery and development in neurodegenerative diseases.