New histone tag discovery offers hope for myelin repair in neurodegenerative diseases

In a groundbreaking study, researchers at the CUNY Graduate Center’s Advanced Science Research Center (CUNY ASRC) have identified a distinct histone tag in mature oligodendrocyte progenitor cells (OPCs) that could pave the way for innovative therapies targeting myelin repair, a critical target for various neurodegenerative and psychiatric disorders, including multiple sclerosis, Alzheimer’s disease and schizophrenia. The histone tag, characterized by lysine 8 acetylation on histone H4, identifies a significant deviation from the histone modifications found in neonatal OPCs.

Detailed in a recently published article in The Journal of Cell Biology (DOI: 10.1083/jcb.202308064), the discovery of this unique histone tag in adult OPCs addresses a long-standing challenge in neurobiology: the inability to translate findings from neonatal OPCs into effective brain therapies for adults. Unlike their neonatal counterparts, adult OPCs exhibit a histone modification that appears to regulate their proliferation, a crucial factor for generating a collection of stem-like cells that can develop into mature oligodendrocytes that produce new myelin; the protective sheath surrounding nerve fibers that is often damaged in neurodegenerative and psychiatric diseases.

Key findings:

• Distinct Histone Tag: The study highlights the acetylation of lysine 8 on histone H4 as an important marker in adult OPCs, distinguishing them from neonatal OPCs.
• Implications for myelin repair: Understanding this regulatory mechanism opens new avenues for developing targeted therapies aimed at promoting myelin repair in the adult brain.

“The identification of this histone tag provides a clearer understanding of OPC proliferation in the adult brain, and it also holds promise for developing more effective therapies for conditions characterized by myelin damage such as multiple sclerosis, Alzheimer’s disease and various psychiatric disorders,” the study said. principal investigator Patrizia Casaccia, founding director of the CUNY ASRC Neuroscience Initiative and Einstein Professor of Biology and Biochemistry at the CUNY Graduate Center. “By focusing on OPCs for adults, we can get closer to repairing myelin damage and improving patient outcomes.”

Our findings underscore the importance of targeting adult-specific cellular mechanisms in neurotherapeutic research.”

David K. Dansu, Ph.D., co-first author of the paper, former PhD researcher in biochemistry at the CUNY ASRC Neuroscience Initiative

“Our future studies will aim to further elucidate the role of lysine 8 acetylation on histone H4 and explore its potential in clinical applications,” said co-first author and Graduate Center biochemistry Ph.D. student Ipek Selcen, also with the CUNY ASRC Neuroscience Initiative.

This research is supported by the National Institute of Neurological Disorders and Stroke at NIH. Additional research support was provided by the CUNY ASRC Epigenetics Core lab and the Proteomic Core lab at NYU.