Pharmacologie clinique et biopharmaceutique

Abstrait

Histone Deacetylase Inhibitor for Neurodegenerative Diseases: A Possible Medicinal Strategy by Prevention of ER Stress-Mediated Apoptosis and Induction of Neurite Elongation

Koji Shimoke, Takuma Tomioka, Kouta Okamoto, Daichi Fujiki, Shinichi Uesato, Hitoshi Nakayama and Toshihiko Ikeuchi

Neurite outgrowth is primarily necessary step to construct a neuronal network. If this step is collapsed, neurons are died and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, which are known to induce endoplasmic reticulum (ER) stress-mediated apoptosis, are occurred.
It has been elucidating that histone deacetylase (HDAC) plays a crucial role in the silencing of gene expression by the specific mechanisms. Thus, HDAC inhibitors have been shown to induce specific genes. We reported the upregulation of the nur77 gene, followed by histone modification via the protein kinase A signaling pathway or HDAC inhibitor-mediated molecular mechanisms. Then, we also focused on neurite outgrowth as a functional neuronal marker, and then described molecular targets and progressive pharmaceutical care for neurodegenerative disorders by using K-350. We propose that this kind of the candidate compound might contribute to build the therapeutic strategy for neurodegenerative diseases.