Introduction: Neurological diseases with a complex etiology and diagnostic complexities are one of the major causes of disability and death globally. In previous preclinical studies, it has been shown that parthenolide (PTL) can provide significant neuroprotective potential. The review synthesizes the mechanistic data on PTL that explains the routes to therapy and creates a strong theoretical framework for future research and drug development. Methods: This review has done a literature search in databases of PubMed, Web of Science, China Science Periodical Database, and China National Knowledge Infrastructure for preclinical studies on PTL. The search terms used were “Parthenolide” and “Nervous System Diseases” as well as specific names of the diseases. We reviewed the mechanistic understanding on PTL of the available literature. Results: PTL inhibits the pathogenesis and development of neurological disease via a wide variety of mechanisms, such as an anti-inflammatory effect, an anti-oxidative stress effect, a reduction of neuronal apoptosis, and the relief of neuropathic pain. Since it addresses more than one pathway in the multifactorial pathological network of neurological illnesses, PTL may have synergistic or additive therapeutic benefits. Discussion: Multi-target therapeutic effects of PTL are effective in combating the interrelated pathological conditions of neurological disorders, whereas derivatives developed according to the structure-activity relationship (SAR) of PTL have additional potential to be clinically translated. Nevertheless, the existing data come mostly in the form of preclinical models, and their translation into clinical practice remains to be confirmed. Conclusion: PTL is a therapeutic agent with great promise in treating neurological disorders. Nevertheless, its potential as a translational drug also requires additional study and confirmation.
Jiang et al. (Thu,) studied this question.