期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
卷 1799, 期 10-12, 页码 840-853出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagrm.2010.08.012
关键词
Neurodegenerative disease; Memory; Histone acetyltransferase; Acetylation; Neuronal death; CREB-binding protein
资金
- Federation de la Recherche sur le Cerveau (FRC)
- Institut National de la Sante et de la Recherche Medicate (INSERM)
- Association pour la Recherche sur les Maladies Neurodegeneratives (AREMANE) [U692]
- University of Strasbourg
- CNRS [FRE 3289]
- Fondation pour la Recherche Medicate (FRM)-Alsace
- IFR 37 Neurosciences (Strasbourg, France)
- Department of Biotechnology, Government of India
Neurodegenerative diseases, such as polyglutamine-related diseases, amyotrophic lateral sclerosis, and Alzheimer's disease are accompanied by transcriptional dysfunctions, leading to neuronal death. It is becoming more evident that the chromatin acetylation status is impaired during the lifetime of neurons, by a common mechanism related to the loss of function of histone acetyltransferase (HAT) activity. Notably, the HAT termed cAMP response element binding protein (CREB) binding protein (CBP) was shown to display neuroprotective functions. Several other HATs have now been shown to participate in basic but vital neuronal functions. In addition, there is increasing evidence of several HATs (including CBP), as essential regulators of neuronal plasticity and memory formation processes. In order to counteract neuronal loss and/or memory deficits in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules antagonizing histone deacetylase (HDAC) activity (i.e. HDAC inhibitors). Although this strategy lacks specificity, some of these molecules display promising therapeutic properties. With the rapidly evolving literature on HATs and their respective functions in neuronal survival and memory formation, it seems essential to envisage direct stimulation of the acetyltransferase function as a new therapeutic tool in neurodegenerative diseases. In this review, we will highlight the present understanding and the future prospects of such therapeutic approach. (C) 2010 Elsevier B.V. All rights reserved.
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