The "normal" Brain. "Abnormal" Ubiquitinilated Deposits Highlight an Age-related Protein Change

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1989 Oct 1

PMID 2552809

Citations 11

Authors

M A Pappolla

R Omar

B Saran

Affiliations

Soon will be listed here.

Abstract

Known morphologic changes that characterize "normal" brain senescence are insufficient to explain the widespread, age-related decline of psychomotor functions. We report that the heavily ubiquitinilated deposits can be consistently detected by immunohistochemistry in the normal senescent brain. Immunostaining of hippocampal sections from aged brains with an anti-ubiquitin antibody was unrelated to neurofibrillary degeneration or senile plaque formation. In contrast, ubiquitin deposits were not detectable in brain sections from neurologically and neuropathologically normal young individuals who had died of nonneurological causes. This finding shows an unrecognized protein change in the normal aged brain.

Citing Articles

Brain aging in acquired immunodeficiency syndrome: increased ubiquitin-protein conjugate is correlated with decreased synaptic protein but not amyloid plaque accumulation.

Gelman B, Schuenke K J Neurovirol. 2004; 10(2):98-108.

PMID: 15204928 DOI: 10.1080/13550280490279816.

Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: relevance to neurodegenerative disease.

Omar R, Pappolla M Eur Arch Psychiatry Clin Neurosci. 1993; 242(5):262-7.

PMID: 8499494 DOI: 10.1007/BF02190384.

Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients.

Nihei K, McKee A, Kowall N Acta Neuropathol. 1993; 86(1):55-64.

PMID: 8396837 DOI: 10.1007/BF00454899.

Two distinct ubiquitin immunoreactive senile plaques in Alzheimer's disease: relationship with the intellectual status in 29 cases.

He Y, Delaere P, Duyckaerts C, Wasowicz M, Piette F, Hauw J Acta Neuropathol. 1993; 86(1):109-16.

PMID: 8396836 DOI: 10.1007/BF00454909.

Markers of axonal injury in post mortem human brain.

Sherriff F, Bridges L, Gentleman S, Sivaloganathan S, Wilson S Acta Neuropathol. 1994; 88(5):433-9.

PMID: 7847072 DOI: 10.1007/BF00389495.

References

Pine M . Metabolic control of intracellular proteolysis in growing and resting cells of Escherichia coli. J Bacteriol. 1966; 92(4):847-50. PMC: 276343. DOI: 10.1128/jb.92.4.847-850.1966. View

Bancher C, Lassmann H, Budka H, Jellinger K, Grundke-Iqbal I, Iqbal K . An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination. J Neuropathol Exp Neurol. 1989; 48(1):81-93. DOI: 10.1097/00005072-198901000-00007. View

Shelanski M, Gaskin F, Cantor C . Microtubule assembly in the absence of added nucleotides. Proc Natl Acad Sci U S A. 1973; 70(3):765-8. PMC: 433354. DOI: 10.1073/pnas.70.3.765. View

GOLDBERG A, Dice J . Intracellular protein degradation in mammalian and bacterial cells. Annu Rev Biochem. 1974; 43(0):835-69. DOI: 10.1146/annurev.bi.43.070174.004155. View

Robinson A, Rudd C . Deamidation of glutaminyl and asparaginyl residues in peptides and proteins. Curr Top Cell Regul. 1974; 8(0):247-95. DOI: 10.1016/b978-0-12-152808-9.50013-4. View

GOLDBERG A, St John A . Intracellular protein degradation in mammalian and bacterial cells: Part 2. Annu Rev Biochem. 1976; 45:747-803. DOI: 10.1146/annurev.bi.45.070176.003531. View

DREYFUS J, Kahn A, SCHAPIRA F . Posttranslational modifications of enzymes. Curr Top Cell Regul. 1978; 14:243-97. DOI: 10.1016/b978-0-12-152814-0.50010-1. View

McKerrow J . Non-enzymatic, post-translational, amino acid modifications in ageing. A brief review. Mech Ageing Dev. 1979; 10(6):371-7. DOI: 10.1016/0047-6374(79)90019-8. View

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

10.

Henderson G, Tomlinson B, Gibson P . Cell counts in human cerebral cortex in normal adults throughout life using an image analysing computer. J Neurol Sci. 1980; 46(1):113-36. DOI: 10.1016/0022-510x(80)90048-9. View

11.

Monnier V, Cerami A . Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science. 1981; 211(4481):491-3. DOI: 10.1126/science.6779377. View

12.

Hsu S, RAINE L, FANGER H . The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol. 1981; 75(6):816-21. DOI: 10.1093/ajcp/75.6.816. View

13.

Fucci L, Oliver C, Coon M, Stadtman E . Inactivation of key metabolic enzymes by mixed-function oxidation reactions: possible implication in protein turnover and ageing. Proc Natl Acad Sci U S A. 1983; 80(6):1521-5. PMC: 393633. DOI: 10.1073/pnas.80.6.1521. View

14.

Hershko A, Heller H, Elias S, Ciechanover A . Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem. 1983; 258(13):8206-14. View

15.

Hershko A . Ubiquitin: roles in protein modification and breakdown. Cell. 1983; 34(1):11-2. DOI: 10.1016/0092-8674(83)90131-9. View

16.

Gafni A, Noy N . Age-related effects in enzyme catalysis. Mol Cell Biochem. 1984; 59(1-2):113-29. DOI: 10.1007/BF00231308. View

17.

Wiederanders B, Oelke B . Accumulation of inactive cathepsin D in old rats. Mech Ageing Dev. 1984; 24(3):265-71. DOI: 10.1016/0047-6374(84)90112-x. View

18.

Finley D, Ciechanover A, Varshavsky A . Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell. 1984; 37(1):43-55. DOI: 10.1016/0092-8674(84)90299-x. View

19.

Omar R, Lanks K . Heat shock protein synthesis and cell survival in clones of normal and simian virus 40-transformed mouse embryo cells. Cancer Res. 1984; 44(9):3976-82. View

20.

Hershko A, Heller H, Eytan E, Kaklij G, Rose I . Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown. Proc Natl Acad Sci U S A. 1984; 81(22):7021-5. PMC: 392068. DOI: 10.1073/pnas.81.22.7021. View