Abstract
Gradual disclosure of the molecular basis of selective neuronal apoptosis during neurodegenerative diseases reveals active participation of acetylating and deacetylating agents during the process. Several studies have now successfully manipulated neuronal vulnerability by influencing the dose and enzymatic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), enzymes regulating acetylation homeostasis within the nucleus, thus focusing on the importance of balanced acetylation status in neuronal vitality. It is now increasingly becoming clear that acetylation balance is greatly impaired during neurodegenerative conditions. Herein, we attempt to illuminate molecular means by which such impairment is manifested and how the compromised acetylation homeostasis is intimately coupled to neurodegeneration. Finally, we discuss the therapeutic potential of reinstating the HAT–HDAC balance to ameliorate neurodegenerative diseases.
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Abbreviations
- AD:
-
Alzheimer's disease
- CaMK:
-
calcium/calmodulin-dependent kinase
- CBP:
-
CREB binding protein
- CDK:
-
cyclin-dependent kinase
- CRE:
-
cAMP-response element
- CREB:
-
cAMP-response element binding (protein)
- HAT:
-
histone acetyltransferase
- HD:
-
Huntington's disease
- HDAC:
-
histone deacetylase
- HIF:
-
hypoxia-induced factor
- IκB:
-
inhibitory kappaB
- MAPK:
-
mitogen-activated protein kinase
- NaBu:
-
sodium butyrate
- NF-κB:
-
nuclear factor kappaB
- NGF:
-
nerve growth factor
- NMDA:
-
N-methyl-D-aspartate
- P/CAF:
-
p300/CBP-associated factor
- PKA:
-
protein kinase A
- PML:
-
promyelocytic leukemia
- REST:
-
repressor element transcription factor
- RPD3:
-
reduced potassium deficiency3
- SAHA:
-
suberoylanilide hydroxamic acid
- SMA:
-
spinal muscular atrophy
- SMM:
-
small molecule modulators
- SP:
-
specificity protein
- TAD:
-
transactivation domain
- TF:
-
transcription factor
- TSA:
-
trichostatin A
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Acknowledgements
This study was supported by grants from NIH (NS39940 and AG19487), National Multiple Sclerosis Society (RG3422A1/1), and Michael J Fox Foundation for Parkinson Research to KP and UNMC graduate assistantship to RNS. We thank V Yennu of MD Anderson, TX, for his support in literature research.
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Saha, R., Pahan, K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ 13, 539–550 (2006). https://doi.org/10.1038/sj.cdd.4401769
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DOI: https://doi.org/10.1038/sj.cdd.4401769
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