No More Brain Tangles with DeltaNp73

Overview

Journal Trends Biochem Sci

Specialty Biochemistry

Date 2008 Nov 15

PMID 19008105

Citations 5

Authors

Mark P Mattson

Uri Ashery

Affiliations

Soon will be listed here.

Abstract

In Alzheimer's disease (AD), neurons suffer dysfunction and death associated with aberrant tau phosphorylation and subsequent neurofibrillary tangles. A new study reveals a surprising neuroprotective role for a truncated p73 isoform (DeltaNp73). Aged mice with reduced DeltaNp73 levels exhibit tau pathology and cognitive deficits, and DeltaNp73 reduction in mice with amyloid pathology causes extensive tangle formation and neuron death. These findings provide a novel animal model of AD and a potential therapeutic role for DeltaNp73 inducers.

Citing Articles

Δ133p53α Protects Human Astrocytes from Amyloid-beta Induced Senescence and Neurotoxicity.

Ungerleider K, Beck J, Lissa D, Joruiz S, Horikawa I, Harris C Neuroscience. 2022; 498:190-202.

PMID: 35716965 PMC: 9420812. DOI: 10.1016/j.neuroscience.2022.06.004.

p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile.

Agostini M, Niklison-Chirou M, Annicchiarico-Petruzzelli M, Grelli S, Di Daniele N, Pestlikis I Mol Neurobiol. 2017; 55(4):3237-3250.

PMID: 28478509 DOI: 10.1007/s12035-017-0517-3.

Diallyl disulfide attenuated carbon ion irradiation-induced apoptosis in mouse testis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway.

Di C, Han L, Zhang H, Xu S, Mao A, Sun C Sci Rep. 2015; 5:16020.

PMID: 26526304 PMC: 4630619. DOI: 10.1038/srep16020.

Mechanisms, function and clinical applications of DNp73.

Di C, Yang L, Zhang H, Ma X, Zhang X, Sun C Cell Cycle. 2013; 12(12):1861-7.

PMID: 23708520 PMC: 3735700. DOI: 10.4161/cc.24967.

Role of p73 in Alzheimer disease: lack of association in mouse models or in human cohorts.

Vardarajan B, Vergote D, Tissir F, Logue M, Yang J, Daude N Mol Neurodegener. 2013; 8:10.

PMID: 23414597 PMC: 3614544. DOI: 10.1186/1750-1326-8-10.

References

Halagappa V, Guo Z, Pearson M, Matsuoka Y, Cutler R, LaFerla F . Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007; 26(1):212-20. DOI: 10.1016/j.nbd.2006.12.019. View

de la Monte S, Sohn Y, Wands J . Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer's disease. J Neurol Sci. 1997; 152(1):73-83. DOI: 10.1016/s0022-510x(97)00131-7. View

Jacobs W, Walsh G, Miller F . Neuronal survival and p73/p63/p53: a family affair. Neuroscientist. 2004; 10(5):443-55. DOI: 10.1177/1073858404263456. View

Walsh G, Orike N, Kaplan D, Miller F . The invulnerability of adult neurons: a critical role for p73. J Neurosci. 2004; 24(43):9638-47. PMC: 6730156. DOI: 10.1523/JNEUROSCI.1299-04.2004. View

Gilman C, Chan S, Guo Z, Zhu X, Greig N, Mattson M . p53 is present in synapses where it mediates mitochondrial dysfunction and synaptic degeneration in response to DNA damage, and oxidative and excitotoxic insults. Neuromolecular Med. 2003; 3(3):159-72. DOI: 10.1385/NMM:3:3:159. View

Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J . p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature. 2000; 404(6773):99-103. DOI: 10.1038/35003607. View

Culmsee C, Mattson M . p53 in neuronal apoptosis. Biochem Biophys Res Commun. 2005; 331(3):761-77. DOI: 10.1016/j.bbrc.2005.03.149. View

De Laurenzi V, Raschella G, Barcaroli D, Annicchiarico-Petruzzelli M, Ranalli M, Catani M . Induction of neuronal differentiation by p73 in a neuroblastoma cell line. J Biol Chem. 2000; 275(20):15226-31. DOI: 10.1074/jbc.275.20.15226. View

Brynczka C, Labhart P, Merrick B . NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation. BMC Genomics. 2007; 8:139. PMC: 1894799. DOI: 10.1186/1471-2164-8-139. View

10.

Wetzel M, Naska S, Laliberte C, Rymar V, Fujitani M, Biernaskie J . p73 regulates neurodegeneration and phospho-tau accumulation during aging and Alzheimer's disease. Neuron. 2008; 59(5):708-21. DOI: 10.1016/j.neuron.2008.07.021. View

11.

Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung C . TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev. 2008; 22(19):2677-91. PMC: 2559903. DOI: 10.1101/gad.1695308. View

12.

McGowan E, Eriksen J, Hutton M . A decade of modeling Alzheimer's disease in transgenic mice. Trends Genet. 2006; 22(5):281-9. DOI: 10.1016/j.tig.2006.03.007. View

13.

Lee A, Ho D, Zanassi P, Walsh G, Kaplan D, Miller F . Evidence that DeltaNp73 promotes neuronal survival by p53-dependent and p53-independent mechanisms. J Neurosci. 2004; 24(41):9174-84. PMC: 6730077. DOI: 10.1523/JNEUROSCI.1588-04.2004. View

14.

Culmsee C, Zhu X, Yu Q, Chan S, Camandola S, Guo Z . A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide. J Neurochem. 2001; 77(1):220-8. DOI: 10.1046/j.1471-4159.2001.t01-1-00220.x. View

15.

Rosso S, Sussman D, Wynshaw-Boris A, Salinas P . Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development. Nat Neurosci. 2004; 8(1):34-42. DOI: 10.1038/nn1374. View

16.

Mattson M . Pathways towards and away from Alzheimer's disease. Nature. 2004; 430(7000):631-9. PMC: 3091392. DOI: 10.1038/nature02621. View

17.

Hooper C, Meimaridou E, Tavassoli M, Melino G, Lovestone S, Killick R . p53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells. Neurosci Lett. 2007; 418(1):34-7. PMC: 1885960. DOI: 10.1016/j.neulet.2007.03.026. View

18.

Scappini E, Koh T, Martin N, OBryan J . Intersectin enhances huntingtin aggregation and neurodegeneration through activation of c-Jun-NH2-terminal kinase. Hum Mol Genet. 2007; 16(15):1862-71. DOI: 10.1093/hmg/ddm134. View

19.

Zhang Y, McLaughlin R, Goodyer C, Leblanc A . Selective cytotoxicity of intracellular amyloid beta peptide1-42 through p53 and Bax in cultured primary human neurons. J Cell Biol. 2002; 156(3):519-29. PMC: 2173346. DOI: 10.1083/jcb.200110119. View

20.

Iqbal K, Alonso A, Chen S, Chohan M, El-Akkad E, Gong C . Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta. 2004; 1739(2-3):198-210. DOI: 10.1016/j.bbadis.2004.09.008. View