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

Advanced Science Research Center, GC/CUNYAug 12 2024

In a groundbreaking study, researchers with the Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC) have identified a distinct histone tag in adult oligodendrocyte progenitor cells (OPCs) that may pave the way for innovative therapies targeting myelin repair, a critical target for several 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 departure from the histone modifications found in neonatal OPCs.

Detailed in a newly published paper 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 to effective adult brain therapies. Unlike their neonatal counterparts, adult OPCs exhibit a histone modification that appears to regulate their proliferation, a crucial factor for generating a pool of stem-like cells capable of developing into mature oligodendrocytes that produce new myelin -; the protective sheath around nerve fibers that is often damaged in neurodegenerative and psychiatric diseases.

Key findings:

• Distinct Histone Tag: The study highlights lysine 8 acetylation on histone H4 as a key 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 like multiple sclerosis, Alzheimer's, and several psychiatric disorders," said the study's 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 adult OPCs, we can move 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., the paper's co-first author, a former biochemistry doctoral student researcher with the CUNY ASRC Neuroscience Initiative

"Our future investigations 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.