[3] Neddylation is essential for human cells, but it becomes aberrant in many pathological processes, such as cancer, neurodegenerative disorders and metabolic diseases.
[4] Neddylation is involved in the pathogenesis of Alzheimer's disease where its activation appears to drive neurons into apoptosis by initiating cell cycle reentry.
[5] Also, evidence suggests that increased NEDD8 conjugation in human oral carcinoma cells leads to abnormal, higher degrees of proliferation.
Higher levels of NEDD8 are found in tumor tissues compared to their normal healthy counterparts, and this is associated with worse prognosis and advanced stages in many cancer types.
Pevonedistat or MLN4929 is the first neddylation E1 inhibitor being tested for several clinical trials in cancer patients, both as a monotherapy and in combination with other therapies.