Protein nitrosylation a process by which redox reactions of nitric oxide (NO) and proteins result in covalent modification of the sulfur in the amino acid cysteine resulting in S-nitrosothiol (SNO). In this episode I talk with Scripps Research Professor Stuart Lipton about his research career highlighting the discovery that protein nitrosylation occurs on numerous proteins in neurons and contributes to the dysfunction and degeneration of neurons in Alzheimer's disease and other neurodegenerative disorders. Prior to his discovery of protein nitrosylation, Stuart worked to better understand the process of excitotoxicity which is involved in the demise of neurons in many neurological disorders. This work led to the development of the only drug – memantine – that slows the progression of Alzheimer's disease, albeit only somewhat. Recently, Stuart was awarded a grant to elucidate the effects of air pollution on the brain with a focus on the role of chemical reactions resulting in protein nitrosylation. Stuart and his team are now working to develop drugs that specifically prevent the chemical reactions that result in excessive protein nitrosylation as treatments for neurodegenerative disorders.

LINKS

Lipton's page at the Scripps:

https://www.scripps.edu/faculty/lipton/

Review articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC11624102/pdf/nihms-2029640.pdf

https://www.nature.com/articles/nrd1958

Original research articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11892585/pdf/pnas.202418179.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC2823371/pdf/nihms173661.pdf