Targeting histone-modifications in Alzheimer's disease. What is the evidence that this is a promising therapeutic avenue?
Alzheimer' s disease (AD) is the most common form of dementia causing an increasing emotional and economical burden to our societies. Although much progress has been made regarding the molecular mechanisms that underlie AD pathogenesis effective therapies are not available yet. The emerging field of neuroepigenetics has provided evidence that de-regulation of epigenetic processes play a role in AD. In this article we will critically review the primary research data that led to the hypothesis that targeting histone-modifying enzymes could be used to treat AD pathogenesis and address the question if the field is ready to translate such findings into clinical application.
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany; Research Group for Epigenetic Mechansims of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany. Electronic address: afische2@gwdg.de.
Andre
A
Fischer
D000107:Acetylation / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D056466:Histone Demethylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation / Q000187:drug effects; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases
Alzheimer; Gene-expression; HDAC inhibitors; Histone-acetylation; Memomry