Metallotexaphyrins As MRI-Active Catalytic Antioxidants for Neurodegenerative Disease: A Study on Alzheimer's Disease

Overview

Journal Chem

Publisher Elsevier

Date 2020 Mar 24

PMID 32201749

Citations 4

Authors

James T Brewster 2nd

Gregory D Thiabaud

Peter Harvey

Hadiqa Zafar

James F Reuther

Simone DellAcqua

Rachel M Johnson

Harrison D Root

Pedro Metola

Alan Jasanoff

Luigi Casella

Jonathan L Sessler

Affiliations

Soon will be listed here.

Abstract

The complex etiology of neurodegeneration continues to stifle efforts to develop effective therapeutics. New agents elucidating key pathways causing neurodegeneration might serve to increase our understanding and potentially lead to improved treatments. Here, we demonstrate that a water-soluble manganese(II) texaphyrin (MMn) is a suitable magnetic resonance imaging (MRI) contrast agent for detecting larger amyloid beta constructs. The imaging potential of MMn was inferred on the basis of studies and detection in Alzheimer's disease models via MRI and ICP-MS. antioxidant- and cellular-based assays provide support for the notion that this porphyrin analog shows promise as a therapeutic agent able to mitigate the oxidative and nitrative toxic effects considered causal in neurodegeneration. The present report marks the first elaboration of an MRI-active metalloantioxidant that confers diagnostic and therapeutic benefit in Alzheimer's disease models without conjugation of a radioisotope, targeting moiety, or therapeutic payload.

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References

Dos Santos Picanco L, Ozela P, Brito M, Pinheiro A, Padilha E, Braga F . Alzheimer's Disease: A Review from the Pathophysiology to Diagnosis, New Perspectives for Pharmacological Treatment. Curr Med Chem. 2018; 25(26):3141-3159. DOI: 10.2174/0929867323666161213101126. View

Fan Y, Wu D, Yi X, Tang H, Wu L, Xia Y . TMPyP Inhibits Amyloid-β Aggregation and Alleviates Amyloid-Induced Cytotoxicity. ACS Omega. 2018; 2(8):4188-4195. PMC: 6044923. DOI: 10.1021/acsomega.7b00877. View

Shimanovich R, Hannah S, Lynch V, Gerasimchuk N, Mody T, Magda D . Mn(II)-texaphyrin as a catalyst for the decomposition of peroxynitrite. J Am Chem Soc. 2001; 123(15):3613-4. DOI: 10.1021/ja005856i. View

Mangialasche F, Polidori M, Monastero R, Ercolani S, Camarda C, Cecchetti R . Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment. Ageing Res Rev. 2009; 8(4):285-305. DOI: 10.1016/j.arr.2009.04.002. View

Kereiakes D, Szyniszewski A, Wahr D, Herrmann H, Simon D, Rogers C . Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term.... Circulation. 2003; 108(11):1310-5. DOI: 10.1161/01.CIR.0000087602.91755.19. View

Kummer M, Hermes M, Delekarte A, Hammerschmidt T, Kumar S, Terwel D . Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation. Neuron. 2011; 71(5):833-44. DOI: 10.1016/j.neuron.2011.07.001. View

Thiabaud G, Pizzocaro S, Garcia-Serres R, Latour J, Monzani E, Casella L . Heme binding induces dimerization and nitration of truncated β-amyloid peptide Aβ16 under oxidative stress. Angew Chem Int Ed Engl. 2013; 52(31):8041-4. DOI: 10.1002/anie.201302989. View

Batinic-Haberle I, Benov L, Spasojevic I, Fridovich I . The ortho effect makes manganese(III) meso-tetrakis(N-methylpyridinium-2-yl)porphyrin a powerful and potentially useful superoxide dismutase mimic. J Biol Chem. 1998; 273(38):24521-8. DOI: 10.1074/jbc.273.38.24521. View

Monzani E, Nicolis S, DellAcqua S, Capucciati A, Bacchella C, Zucca F . Dopamine, Oxidative Stress and Protein-Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases. Angew Chem Int Ed Engl. 2018; 58(20):6512-6527. DOI: 10.1002/anie.201811122. View

10.

Dostal V, Link C . Assaying β-amyloid toxicity using a transgenic C. elegans model. J Vis Exp. 2010; (44). PMC: 3185644. DOI: 10.3791/2252. View

11.

Zhang X, Zhou W, Zhang Y . Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant. Mil Med Res. 2018; 5(1):30. PMC: 6125955. DOI: 10.1186/s40779-018-0176-3. View

12.

Hiner A, Raven E, Thorneley R, Garcia-Canovas F, Rodriguez-Lopez J . Mechanisms of compound I formation in heme peroxidases. J Inorg Biochem. 2002; 91(1):27-34. DOI: 10.1016/s0162-0134(02)00390-2. View

13.

Thiabaud G, McCall R, He G, Arambula J, Siddik Z, Sessler J . Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator. Angew Chem Int Ed Engl. 2016; 55(41):12626-31. PMC: 5039070. DOI: 10.1002/anie.201604236. View

14.

Gitler A, Dhillon P, Shorter J . Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech. 2017; 10(5):499-502. PMC: 5451177. DOI: 10.1242/dmm.030205. View

15.

Bolognesi M, Gandini A, Prati F, Uliassi E . From Companion Diagnostics to Theranostics: A New Avenue for Alzheimer's Disease?. J Med Chem. 2016; 59(17):7759-70. DOI: 10.1021/acs.jmedchem.6b00151. View

16.

Arneson D, Zhang Y, Yang X, Narayanan M . Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks. J Genet. 2018; 97(3):795-806. PMC: 6211183. View

17.

Ghosh C, Seal M, Mukherjee S, Dey S . Alzheimer's Disease: A Heme-Aβ Perspective. Acc Chem Res. 2015; 48(9):2556-64. DOI: 10.1021/acs.accounts.5b00102. View

18.

Parikshak N, Gandal M, Geschwind D . Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders. Nat Rev Genet. 2015; 16(8):441-58. PMC: 4699316. DOI: 10.1038/nrg3934. View

19.

Gross Z . High-valent corrole metal complexes. J Biol Inorg Chem. 2001; 6(7):733-8. DOI: 10.1007/s007750100273. View

20.

Albert R . Scale-free networks in cell biology. J Cell Sci. 2005; 118(Pt 21):4947-57. DOI: 10.1242/jcs.02714. View