Phenylbutyrate is a multifaceted drug that exerts neuroprotective effects and reverses the Alzheimeŕs disease-like phenotype of a commonly used mouse model

Current Pharmaceutical Design

Volumn 19, Issue 28, 2013, Pages 5076-5084

  Cuadrado Tejedor, Mar ^a,b   Ricobaraza, Ana L ^a   Torrijo, Rosana ^a   Franco, Rafael ^a,c   Garcia Osta, Ana ^a  

^a UNIVERSITY OF NAVARRA   (Spain)

^b UNIVERSITY OF NAVARRA   (Spain)

^c UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Amyloid; APP processing; Histone deacetylase; Tau phosphorylation

Indexed keywords

4 PHENYLBUTYRIC ACID; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BUTYRIC ACID; CHAPERONE; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; TAU PROTEIN;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DENSITY; CELL LOSS; CONTROLLED STUDY; DENDRITIC SPINE; DRUG MECHANISM; FEMALE; HIPPOCAMPAL CA1 REGION; HISTONE ACETYLATION; MOUSE; NERVE CELL; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN HOMEOSTASIS; PROTEIN PHOSPHORYLATION; TRANSGENIC MOUSE;

ACETYLATION; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BIOLOGICAL MARKERS; BUTYRIC ACID; CA1 REGION, HIPPOCAMPAL; CELLS, CULTURED; DISEASE MODELS, ANIMAL; FEMALE; HISTONE DEACETYLASE INHIBITORS; HISTONES; MICE; MICE, TRANSGENIC; NEURONS; NEUROPROTECTIVE AGENTS; NOOTROPIC AGENTS; PHENYLBUTYRATES; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; TAU PROTEINS;

EID: 84881357704     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319280006     Document Type: Article

References (49)

1. Saha RN, Pahan K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ 2006; 13: 539-50.
2. Fischer A, Sananbenesi F, Mungenast A, Tsai LH. Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol Sci 2010; 31: 605-17.
3. Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009; 459: 55-60.
4. McQuown SC, Barrett RM, Matheos DP, et al. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci 2011; 31: 764-74.
5. Bahari-Javan S, Maddalena A, Kerimoglu C, et al. HDAC1 regulates fear extinction in mice. J Neurosci 2012; 32: 5062-73.
6. Agis-Balboa RC, Pavelka Z, Kerimoglu C, Fischer A. Loss of HDAC5 Impairs Memory Function: Implications for Alzheimer's Disease. J Alzheimers Dis 2012.
7. Kim MS, Akhtar MW, Adachi M, et al. An essential role for histone deacetylase 4 in synaptic plasticity and memory formation. J Neurosci 2012; 32: 10879-86.
8. Sando R, 3rd, Gounko N, Pieraut S, Liao L, Yates J, 3rd, Maximov A. HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory. Cell 2012; 151: 821-34.
9. Ricobaraza A, Cuadrado-Tejedor M, Perez-Mediavilla A, Frechilla D, Del Rio J, Garcia-Osta A. Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model. Neuropsychopharmacology 2009; 34: 1721-32.
10. Zhang K, Schrag M, Crofton A, Trivedi R, Vinters H, Kirsch W. Targeted proteomics for quantification of histone acetylation in Alzheimer's disease. Proteomics 2012; 12: 1261-8.
11. Francis YI, Fa M, Ashraf H, et al. Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer's disease. J Alzheimers Dis 2009; 18: 131-9.
12. Kilgore M, Miller CA, Fass DM, et al. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology 2010; 35: 870-80.
13. Qing H, He G, Ly PT, et al. Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. J Exp Med 2008; 205: 2781-9.
14. Graff J, Rei D, Guan JS, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012; 483: 222-6.
15. Engmann O, Hortobagyi T, Pidsley R, et al. Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition. Brain 2011; 134: 2408-21.
16. Engmann O, Hortobagyi T, Thompson AJ, et al. Cyclin-dependent kinase 5 activator p25 is generated during memory formation and is reduced at an early stage in Alzheimer's disease. Biol Psychiatry 2011; 70: 159-68.
17. Kim D, Frank CL, Dobbin MM, et al. Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity. Neuron 2008; 60: 803-17.
18. Li G, Jiang H, Chang M, Xie H, Hu L. HDAC6 alpha-tubulin deacetylase: a potential therapeutic target in neurodegenerative diseases. J Neurol Sci 2011; 304: 1-8.
19. Ding H, Dolan PJ, Johnson GV. Histone deacetylase 6 interacts with the microtubule-associated protein tau. J Neurochem 2008; 106: 2119-30.
20. Hempen B, Brion JP. Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer's disease. J Neuropathol Exp Neurol 1996; 55: 964-72.
21. Sung YM, Lee T, Yoon H, et al. Mercaptoacetamide-based class II HDAC inhibitor lowers Abeta levels and improves learning and memory in a mouse model of Alzheimer's disease. Exp Neurol 2012; 239C: 192-201.
22. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 2012; 11: 384-400.
23. Collins AF, Pearson HA, Giardina P, McDonagh KT, Brusilow SW, Dover GJ. Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. Blood 1995; 85: 43-9.
24. Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr 1996; 43: 127-70.
25. Cuadrado-Tejedor M, Garcia-Osta A, Ricobaraza A, Oyarzabal J, Franco R. Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease. Curr Med Chem 2012; 18: 5545-53.
26. Ricobaraza A, Cuadrado-Tejedor M, Marco S, Perez-Otano I, Garcia-Osta A. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus 2012; 22: 1040-50.
27. Ricobaraza A, Cuadrado-Tejedor M, Garcia-Osta A. Long-term phenylbutyrate administration prevents memory deficits in Tg2576 mice by decreasing Abeta. Front Biosci (Elite Ed) 2011; 3: 1375-84.
28. Levenson JM, O'Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 2004; 279: 40545-59.
29. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. Recovery of learning and memory is associated with chromatin remodelling. Nature 2007; 447: 178-82.
30. Govindarajan N, Agis-Balboa RC, Walter J, Sananbenesi F, Fischer A. Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis 2011; 26: 187-97.
31. Kubota K, Niinuma Y, Kaneko M, et al. Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. J Neurochem 2006; 97: 1259-68.
32. Irizarry MC, McNamara M, Fedorchak K, Hsiao K, Hyman BT. APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J Neuropathol Exp Neurol 1997; 56: 965-73.
33. Simon AM, Schiapparelli L, Salazar-Colocho P, et al. Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol Dis 2009; 33: 369-78.
34. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996; 274: 99-102.
35. Cam JA, Zerbinatti CV, Knisely JM, Hecimovic S, Li Y, Bu G. The low density lipoprotein receptor-related protein 1B retains beta-amyloid precursor protein at the cell surface and reduces amyloid-beta peptide production. J Biol Chem 2004; 279: 29639-46.
36. Zhang YW, Thompson R, Zhang H, Xu H. APP processing in Alzheimer's disease. Mol Brain 2011; 4: 3.
37. Rubenstein RC, Zeitlin PL. Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR. Am J Physiol Cell Physiol 2000; 278: C259-67.
38. Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer's disease. J Neurochem 2008; 104: 1433-9.
39. Mandelkow EM, Biernat J, Drewes G, Gustke N, Trinczek B, Mandelkow E. Tau domains, phosphorylation, and interactions with microtubules. Neurobiol Aging 1995; 16: 355-62; discussion 62-3.
40. Mandelkow EM, Drewes G, Biernat J, et al. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett 1992; 314: 315-21.
41. Wiley JC, Pettan-Brewer C, Ladiges WC. Phenylbutyric acid reduces amyloid plaques and rescues cognitive behavior in AD transgenic mice. Aging Cell 2011; 10: 418-28.
42. McGowan E, Eriksen J, Hutton M. A decade of modeling Alzheimer's disease in transgenic mice. Trends Genet 2006; 22: 281-9.
43. Mucke L, Masliah E, Yu GQ, et al. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 2000; 20: 4050-8.
44. Hass S, Weidemann A, Utermann G, Baier G. Intracellular apolipoprotein E affects Amyloid Precursor Protein processing and amyloid Abeta production in COS-1 cells. Mol Genet Genomics 2001; 265: 791-800.
45. Wiley JC, Meabon JS, Frankowski H, et al. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells. PLoS One 2010; 5: e9135.
46. Pajak B, Orzechowski A, Gajkowska B. Molecular basis of sodium butyrate-dependent proapoptotic activity in cancer cells. Adv Med Sci 2007; 52: 83-8.
47. Iannitti T, Palmieri B. Clinical and experimental applications of sodium phenylbutyrate. Drugs R D 2011; 11: 227-49.
48. Kim AJ, Shi Y, Austin RC, Werstuck GH. Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 2005; 118: 89-99.
49. Mimori S, Okuma Y, Kaneko M, et al. Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress. Biol Pharm Bull 2012; 35: 84-90.