Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Immunity & Ageing
Published in: Immunity & Ageing 1/2013

Open Access 01-12-2013 | Research

Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes

Authors: Carolin Cornelius, Angela Trovato Salinaro, Maria Scuto, Vincenzo Fronte, Maria Teresa Cambria, Manuela Pennisi, Rita Bella, Pietro Milone, Antonio Graziano, Rosalia Crupi, Salvatore Cuzzocrea, Giovanni Pennisi, Vittorio Calabrese

Published in: Immunity & Ageing | Issue 1/2013

Login to get access

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder affecting up to one third of individuals reaching the age of 80. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed Vitagenes. Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs). In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.
We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects. Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.
This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.
Appendix
Available only for authorised users
Literature
1.
Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E: Alzheimer’s disease. Lancet. 2011, 19: 1019-1031.CrossRef
2.
3.
Mayeux R, Stern Y: Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med. 2012, 1: 2-8.
4.
Blennow K, De Leon MJ, Zetterberg H: Alzheimer’s disease. Lancet. 2006, 29: 387-403.CrossRef
5.
Gandy S: The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease. J Clin Invest. 2005, 115: 1121-1129.PubMedCentralPubMed
6.
Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I: Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta. 2005, 3 1739 (2–3): 198-210.CrossRef
7.
Katzman R, Saitoh T: Advances in Alzheimer’s disease. FASEB J. 1991, 5: 278-286.PubMed
8.
Keller JN, Hanni KB, Markesbery WR: Impaired proteasome function in Alzheimer’s disease. J Neurochem. 2000, 75: 436-439.CrossRefPubMed
9.
Perry G, Friedman R, Shaw G, Chau V: Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci USA. 1987, 84: 3033-3036. 10.1073/pnas.84.9.3033.PubMedCentralCrossRefPubMed
10.
Holscher C: Development of beta-amyloid-induced neurodegeneration in Alzheimer’s disease and novel neuroprotective strategies. Rev Neurosci. 2005, 16: 181-212.CrossRefPubMed
11.
Dumont M, Wille E, Stack C, Calingasan NY, Beal MF, Lin MT: Reduction of oxidative stress, amyloid deposition, and memory deficit by manganese superoxide dismutase overexpression in a transgenic mouse model of Alzheimer’s disease. FASEB J. 2009, 23: 2459-2466. 10.1096/fj.09-132928.PubMedCentralCrossRefPubMed
12.
Maarten E, Witte John GJM, Bol Wouter H, Gerritsen P, van der Valk B, Drukarch J, Van Horssen M, Wilhelmus MM: Parkinson’s disease-associated parkin colocalizes with Alzheimer’s disease and multiple sclerosis brain lesions. Neurobiol Dis. 2009, 15: 1150-1161.
13.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology. 1984, 34: 939-944. 10.1212/WNL.34.7.939.CrossRefPubMed
14.
Butterfield DA, Drake J, Pocernich C, Castegna A: Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptid. Trends Mol Med. 2001, 7: 548-554. 10.1016/S1471-4914(01)02173-6.CrossRefPubMed
15.
Calabrese V, Scapagnini G, Giuffrida Stella AM, Bates TE, Clark JB: Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res. 2001, 26: 739-764. 10.1023/A:1010955807739.CrossRefPubMed
16.
Calabrese V, Guagliano E, Sapienza M, Panebianco M, Calafato S, Puleo E: Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of Vitagenes. Neurochem Res. 2007, 32: 757-773. 10.1007/s11064-006-9203-y.CrossRefPubMed
17.
Calabrese V, Cornelius C, Mancuso C, Pennisi G, Calafato S, Bellia F: Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res. 2008, 33: 2444-2471. 10.1007/s11064-008-9775-9.CrossRefPubMed
18.
Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Giuffrida Stella AM: Nitric oxide in the CNS: neuroprotection versus neurotoxicity. Nat Neurosci. 2007, 8: 766-775. 10.1038/nrn2214.CrossRef
19.
Calabrese V, Cornelius C, Stella AM, Calabrese EJ: Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes. Neurochem Res. 2010, 35: 1880-1915. 10.1007/s11064-010-0307-z.CrossRefPubMed
20.
Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J: Sirtuins: the “magnificent seven”, function, metabolism and longevity. Ann Med. 2007, 39: 335-345. 10.1080/07853890701408194.CrossRefPubMed
21.
Calabrese V, Bates TE, Giuffrida Stella AM: NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: the role of oxidant/antioxidant balance. Neurochem Res. 2000, 65: 1315-1341.CrossRef
22.
Calabrese V, Scapagnini G, Ravagna A, Giuffrida Stella AM, Butterfield DA: Molecular chaperones and their roles in neural cell differentiation. Dev Neurosci. 2002, 24: 1-13. 10.1159/000064941.CrossRefPubMed
23.
Calabrese V, Guagliano E, Sapienza M, Mancuso C, Butterfield DA, Stella AM: Redox regulation of cellular stress response in neurodegenerative disorders. Ital J Biochem. 2006, 55: 263-282.PubMed
24.
Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP: Cellular stress responses, the hormesis paradigm, and Vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal. 2010, 13: 1763-1811. 10.1089/ars.2009.3074.PubMedCentralCrossRefPubMed
25.
26.
Kathryn F, Di Trapani T, Di Trapani G: Thioredoxin system inhibitors as mediators of apoptosis for cancer therapy. Mol Nutr Food Res. 2009, 53: 87-103. 10.1002/mnfr.200700492.CrossRef
27.
Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, Miroux B, Couplan E, Alves-Guerra MC, Goubern M, Surwit R, Bouillaud F, Richard D, Collins S, Ricquier DD: Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet. 2000, 26: 435-439. 10.1038/82565.CrossRefPubMed
28.
Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB: Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem. 2000, 275: 16258-16266. 10.1074/jbc.M910179199.CrossRefPubMed
29.
Smith P, Krohn R, Hermanson G, Mallia A, Gartner F, Provenzano M: Measurement of proteins using bicinchoninic acid. Ann Biochem. 1985, 150: 76-85. 10.1016/0003-2697(85)90442-7.CrossRef
30.
Glenner GG, Wong CW: Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984, 120: 885-890. 10.1016/S0006-291X(84)80190-4.CrossRefPubMed
31.
Lee VM, Balin BJ, Otvos JL, Trojanowski JQ: A 68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science. 1991, 251: 675-678. 10.1126/science.1899488.CrossRefPubMed
32.
Selkoe DJ: The molecular pathology of Alzheimer’s disease. Neuron. 1991, 6: 487-498. 10.1016/0896-6273(91)90052-2.CrossRefPubMed
33.
Calabrese V, Butterfield DA, Scapagnini G, Stella AM, Maines MD: Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: relevance to brain aging, neurodegenerative disorders, and longevity. Antioxid Redox Signal. 2006, 8: 444-477. 10.1089/ars.2006.8.444.CrossRefPubMed
34.
Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA: Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: the role of Vitagenes. In Vivo. 2004, 18: 245-267.PubMed
35.
Mancuso C, Scapagnini G, Curro D, Giuffrida Stella AM, De Marco C, Butterfield DA: Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci. 2007, 12: 1107-1123. 10.2741/2130.CrossRefPubMed
36.
Butterfield DA, Lauderback CM: Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med. 2002, 32: 1050-1060. 10.1016/S0891-5849(02)00794-3.CrossRefPubMed
37.
Lauderback CM, Hackett JM, Huang FF, Keller JN, Szweda LI, Markesbery WR, Butterfield DA: The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer’s disease brain: the role of Abeta1-42. J Neurochem. 2001, 78: 413-416. 10.1046/j.1471-4159.2001.00451.x.CrossRefPubMed
38.
Bloomfield KL, Osborne SA, Kennedy DD, Clarke FM, Tonissen KF: Thioredoxin-mediated redox control of the transcription factor Sp1 and regulation of the thioredoxin gene promoter. Gene. 2003, 319: 107-116.CrossRefPubMed
39.
Bonda DJ, Lee HG, Camins A, Pallàs M, Casadesus G, Smith MA, Zhu X: The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic consideration. Lancet Neurol. 2011, 10: 275-279. 10.1016/S1474-4422(11)70013-8.PubMedCentralCrossRefPubMed
40.
Boyd-Kimball D, Sultana R, Mohammad-Abdul H, Butterfield DA: Rodent Abeta (1-42) exhibits oxidative stress properties similar to those of human Abeta (1-42): implications for roposed mechanisms of toxicity. J Alzheimers Dis. 2004, 6: 515-525.PubMed
41.
Boyd-Kimball D, Castegna A, Sultana R, Poon HF, Petroze R, Lynn BC, Klein JB, Butterfield DA: Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes: implications for Alzheimer’s disease. Brain Res. 2005, 1044: 206-215. 10.1016/j.brainres.2005.02.086.CrossRefPubMed
42.
Boyd-Kimball D, Poon HF, Lynn BC, Cai J, Pierce WM, Klein JB, Ferguson J, Link CD, Butterfield DA: Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Aβ 1-42): implications for Alzheimer’s disease. Neurobiol Aging. 2006, 27: 1239-1249. 10.1016/j.neurobiolaging.2005.07.001.CrossRefPubMed
43.
Butterfield DA, Griffin S, Munch G, Pasinetti GM: Amyloid beta-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer’s disease brain exists. J Alzheimers Dis. 2002, 4: 193-201.PubMed
44.
Butterfield DA, Poon HF, Clair D, Keller JN, Pierce WM, Klein JB, Markesbery WR: Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimers disease. Neurobiol Dis. 2006, 22: 223-232. 10.1016/j.nbd.2005.11.002.CrossRefPubMed
45.
Calabrese V, Sultana R, Scapagnini G, Guagliano E, Sapienza M, Bella R, Kanski J, Pennisi G, Mancuso C, Stella AM, Butterfield DA: Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer’s disease. Antioxid Redox Signal. 2006, 8: 1975-1986. 10.1089/ars.2006.8.1975.CrossRefPubMed
46.
Calabrese V, Butterfield DA, Stella AM: Aging and oxidative stress response in the CNS. Neurochem Mol Neurobiol. 2008, 23: 128-234.
47.
De la Monte SM, Wands JR: Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer’s disease. J Alzheimers Dis. 2006, 9: 167-181.PubMed
48.
Drake J, Link CD, Butterfield DA: Oxidative stress precedes fibrillar deposition of Alzheimer’s disease amyloid beta-peptide (1-42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging. 2003, 24: 415-420. 10.1016/S0197-4580(02)00225-7.CrossRefPubMed
49.
50.
Hirota K, Nakamura H, Masutani H, Yodoi J: Thioredoxin superfamily and thioredoxin-inducing agents. Ann NY Acad Sci. 2002, 957: 189-199. 10.1111/j.1749-6632.2002.tb02916.x.CrossRefPubMed
51.
Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR: Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology. 2005, 64: 1152-1156. 10.1212/01.WNL.0000156156.13641.BA.CrossRefPubMed
52.
Nguyen T, Nioi P, Pickett CB: The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009, 284: 13291-13299. 10.1074/jbc.R900010200.PubMedCentralCrossRefPubMed
53.
Vauzour D, Buonfiglio M, Corona G, Chirafisi J, Vafeiadou K, Angeloni C, Hrelia S, Hrelia P, Spencer SP: Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes. Mol Nutr Food Res. 2010, 54: 532-542. 10.1002/mnfr.200900197.CrossRefPubMed
54.
Salminen A, Kauppinen A, Suuronen T, Kaarniranta K: SIRT1 longevity factor suppresses NF-kappaB–driven immune responses: regulation of aging via NF-kappaB acetylation?. Bioessays. 2008, 30: 939-942. 10.1002/bies.20799.CrossRefPubMed
55.
Tanaka T, Nakamura H, Nishiyama A, Hosoi F, Masutani H, Wada H, Yodoi J: Redox regulation by thioredoxin superfamily: protection against oxidative stress and aging. Free Radic Res. 2000, 33: 851-855. 10.1080/10715760000301361.CrossRefPubMed
56.
57.
Prozorovski T, Schulze-Topphoff U, Glumm R, Baumgart J, Schröter F, Ninnemann O: Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol. 2008, 10: 385-394. 10.1038/ncb1700.CrossRefPubMed
58.
Nishiyama A, Masutani H, Nakamura H, Nishinaka Y, Yodoi J: Redox regulation by thioredoxin and thioredoxin-binding proteins. IUBMB Life. 2001, 52: 29-33. 10.1080/15216540252774739.CrossRefPubMed
Metadata
Title
Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes
Authors
Carolin Cornelius
Angela Trovato Salinaro
Maria Scuto
Vincenzo Fronte
Maria Teresa Cambria
Manuela Pennisi
Rita Bella
Pietro Milone
Antonio Graziano
Rosalia Crupi
Salvatore Cuzzocrea
Giovanni Pennisi
Vittorio Calabrese
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2013
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/1742-4933-10-41

Other articles of this Issue 1/2013

Immunity & Ageing 1/2013 Go to the issue

Review

Toll like receptor signaling in “inflammaging”: microRNA as new players

Research

Cytokine and chemokine responses to helminth and protozoan parasites and to fungus and mite allergens in neonates, children, adults, and the elderly

Research

Effects of human Toll-like receptor 1 polymorphisms on ageing

Research

Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011–2012 influenza vaccine season

Review

Mast cells and the liver aging process

Research

Increased activation and cytokine secretion in B cells stimulated with leptin in aged humans
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits