help button home button Am J Pathol Angiogenesis Meeting
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Galvin, J. E.
Right arrow Articles by Trojanowski, J. Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Galvin, J. E.
Right arrow Articles by Trojanowski, J. Q.
(American Journal of Pathology. 2000;157:361-368.)
© 2000 American Society for Investigative Pathology

Short Communications

Neurodegeneration with Brain Iron Accumulation, Type 1 Is Characterized by {alpha}-, ß-, and {gamma}-Synuclein Neuropathology

James E. Galvin*{dagger}, Benoit Giasson{dagger}, Howard I. Hurtig{ddagger}, Virginia M.-Y. Lee{dagger} and John Q. Trojanowski{dagger}

From the Department of Neurology,*
Medical College of Pennsylvania Hahnemann University; the Department of Pathology and Laboratory Medicine,{dagger}
the Center for Neurodegenerative Disease Research, and the Department of Neurology,{ddagger}
the University of Pennsylvania, Philadelphia, Pennsylvania

Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here we show that there is an accumulation of {alpha}-synuclein ({alpha}S) in LB-like inclusions, glial inclusions, and spheroids in the brains of three NBIA 1 patients. Further, ß-synuclein (ßS) and {gamma}-synuclein ({gamma}S) immunoreactivity was detected in spheroids but not in LB-like or glial inclusions. Western blot analysis demonstrated high-molecular weight {alpha}S aggregates in the high-salt-soluble and Triton X-100-insoluble/sodium dodecyl sulfate-soluble fraction of the NBIA 1 brain. Significantly, the levels of {alpha}S were markedly reduced in the Triton X-100-soluble fractions compared to control brain, and unlike other synucleinopathies, insoluble {alpha}S did not accumulate in the formic acid-soluble fraction. These findings expand the concept of neurodegenerative synucleinopathies by implicating {alpha}S, ßS, and {gamma}S in the pathogenesis of NBIA 1.




This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
F. Bosveld, A. Rana, P. E. van der Wouden, W. Lemstra, M. Ritsema, H. H. Kampinga, and O. C. M. Sibon
De novo CoA biosynthesis is required to maintain DNA integrity during development of the Drosophila nervous system
Hum. Mol. Genet., July 1, 2008; 17(13): 2058 - 2069.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
I. Malik, J. Turk, D. J. Mancuso, L. Montier, M. Wohltmann, D. F. Wozniak, R. E. Schmidt, R. W. Gross, and P. T. Kotzbauer
Disrupted Membrane Homeostasis and Accumulation of Ubiquitinated Proteins in a Mouse Model of Infantile Neuroaxonal Dystrophy Caused by PLA2G6 Mutations
Am. J. Pathol., February 1, 2008; 172(2): 406 - 416.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
Y.-h. Sung and D. Eliezer
Secondary structure and dynamics of micelle bound beta- and {gamma}-synuclein
Protein Sci., May 1, 2006; 15(5): 1162 - 1174.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. W. Shults, E. Rockenstein, L. Crews, A. Adame, M. Mante, G. Larrea, M. Hashimoto, D. Song, T. Iwatsubo, K. Tsuboi, et al.
Neurological and Neurodegenerative Alterations in a Transgenic Mouse Model Expressing Human {alpha}-Synuclein under Oligodendrocyte Promoter: Implications for Multiple System Atrophy
J. Neurosci., November 16, 2005; 25(46): 10689 - 10699.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. A. Greenbaum, C. L. Graves, A. J. Mishizen-Eberz, M. A. Lupoli, D. R. Lynch, S. W. Englander, P. H. Axelsen, and B. I. Giasson
The E46K Mutation in {alpha}-Synuclein Increases Amyloid Fibril Formation
J. Biol. Chem., March 4, 2005; 280(9): 7800 - 7807.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. T. Kotzbauer, A. C. Truax, J. Q. Trojanowski, and V. M.-Y. Lee
Altered Neuronal Mitochondrial Coenzyme A Synthesis in Neurodegeneration with Brain Iron Accumulation Caused by Abnormal Processing, Stability, and Catalytic Activity of Mutant Pantothenate Kinase 2
J. Neurosci., January 19, 2005; 25(3): 689 - 698.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Klucken, Y. Shin, E. Masliah, B. T. Hyman, and P. J. McLean
Hsp70 Reduces {alpha}-Synuclein Aggregation and Toxicity
J. Biol. Chem., June 11, 2004; 279(24): 25497 - 25502.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. C. Pawlyk, B. I. Giasson, D. M. Sampathu, F. A. Perez, K. L. Lim, V. L. Dawson, T. M. Dawson, R. D. Palmiter, J. Q. Trojanowski, and V. M.-Y. Lee
Novel Monoclonal Antibodies Demonstrate Biochemical Variation of Brain Parkin with Age
J. Biol. Chem., November 28, 2003; 278(48): 48120 - 48128.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Ninkina, K. Papachroni, D. C. Robertson, O. Schmidt, L. Delaney, F. O'Neill, F. Court, A. Rosenthal, S. M. Fleetwood-Walker, A. M. Davies, et al.
Neurons Expressing the Highest Levels of {gamma}-Synuclein Are Unaffected by Targeted Inactivation of the Gene
Mol. Cell. Biol., November 15, 2003; 23(22): 8233 - 8245.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Golts, H. Snyder, M. Frasier, C. Theisler, P. Choi, and B. Wolozin
Magnesium Inhibits Spontaneous and Iron-induced Aggregation of alpha -Synuclein
J. Biol. Chem., May 3, 2002; 277(18): 16116 - 16123.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pathol.Home page
D J Burn and E Jaros
Multiple system atrophy: cellular and molecular pathology
Mol. Pathol., December 1, 2001; 54(6): 419 - 426.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. J. Kahle, M. Neumann, L. Ozmen, V. Muller, S. Odoy, N. Okamoto, H. Jacobsen, T. Iwatsubo, J. Q. Trojanowski, H. Takahashi, et al.
Selective Insolubility of {alpha}-Synuclein in Human Lewy Body Diseases Is Recapitulated in a Transgenic Mouse Model
Am. J. Pathol., December 1, 2001; 159(6): 2215 - 2225.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. J. Perrin, W. S. Woods, D. F. Clayton, and J. M. George
Exposure to Long Chain Polyunsaturated Fatty Acids Triggers Rapid Multimerization of Synucleins
J. Biol. Chem., November 2, 2001; 276(45): 41958 - 41962.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
B. I. Giasson, J. E. Duda, I. V. J. Murray, Q. Chen, J. M. Souza, H. I. Hurtig, H. Ischiropoulos, J. Q. Trojanowski, and V. M. -Y. Lee
Oxidative Damage Linked to Neurodegeneration by Selective alpha -Synuclein Nitration in Synucleinopathy Lesions
Science, November 3, 2000; 290(5493): 985 - 989.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the American Society for Investigative Pathology.