 |
The Journal of Neuroscience, February 18, 2004, 24(7):1700-1706; doi:10.1523/JNEUROSCI.4330-03.2004
 Previous Article | Next Article 
Cellular/Molecular
Heat Shock Protein 70 Participates in the Neuroprotective Response to Intracellularly Expressed  -Amyloid in Neurons
Jordi Magrané,1,2
Roy C. Smith,2
Kenneth Walsh,2 and
Henry W. Querfurth1
1Division of Neurology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, and 2Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118
Intracellular  -amyloid 42 (A42) accumulation is increasingly recognized as an early event in the pathogenesis of Alzheimer's disease (AD). We have developed a doxycycline-inducible adenoviral-based system that directs intracellular A42 expression and accumulation into the endoplasmic reticulum of primary neuronal cultures in a regulated manner. A42 exhibited a perinuclear distribution in cell bodies and an association with vesicular compartments. Virally expressed intracellular A42 was toxic to neuronal cultures 24 hr after induction in a dose-dependent manner. A42 expression prompted the rapid induction of stress-inducible Hsp70 protein in neurons, and virally mediated Hsp70 overexpression rescued neurons from the toxic effects of intracellular A accumulation. Together, these results implicate the cellular stress response as a possible modulator of A-induced toxicity in neuronal cultures.
Key words: Alzheimer's disease; intracellular; amyloid; adenovirus; neuronal toxicity; stress response
Received Sep 23, 2003;
revised December 31, 2003;
accepted December 31, 2003.
This article has been cited by other articles:
|
|
|
|
 
B. M. Wegenast-Braun, A. Fulgencio Maisch, D. Eicke, R. Radde, M. C. Herzig, M. Staufenbiel, M. Jucker, and M. E. Calhoun
Independent Effects of Intra- and Extracellular A{beta} on Learning-Related Gene Expression
Am. J. Pathol.,
July 1, 2009;
175(1):
271 - 282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Summers, P. M. Douglas, H.-Y. Ren, and D. M. Cyr
The Type I Hsp40 Ydj1 Utilizes a Farnesyl Moiety and Zinc Finger-like Region to Suppress Prion Toxicity
J. Biol. Chem.,
February 6, 2009;
284(6):
3628 - 3639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. King, C. G. Goemans, F. Hafiz, J. H. M. Prehn, A. Wyttenbach, and A. M. Tolkovsky
Cytoplasmic Inclusions of Htt Exon1 Containing an Expanded Polyglutamine Tract Suppress Execution of Apoptosis in Sympathetic Neurons
J. Neurosci.,
December 31, 2008;
28(53):
14401 - 14415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fonte, D. R. Kipp, J. Yerg III, D. Merin, M. Forrestal, E. Wagner, C. M. Roberts, and C. D. Link
Suppression of in Vivo -Amyloid Peptide Toxicity by Overexpression of the HSP-16.2 Small Chaperone Protein
J. Biol. Chem.,
January 11, 2008;
283(2):
784 - 791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Kumar, R. K. Ambasta, V. Veereshwarayya, K. M. Rosen, K. S. Kosik, H. Band, R. Mestril, C. Patterson, and H. W. Querfurth
CHIP and HSPs interact with {beta}-APP in a proteasome-dependent manner and influence A{beta} metabolism
Hum. Mol. Genet.,
April 1, 2007;
16(7):
848 - 864.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. G. Evans, S. Wisen, and J. E. Gestwicki
Heat Shock Proteins 70 and 90 Inhibit Early Stages of Amyloid beta-(1-42) Aggregation in Vitro
J. Biol. Chem.,
November 3, 2006;
281(44):
33182 - 33191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Veereshwarayya, P. Kumar, K. M. Rosen, R. Mestril, and H. W. Querfurth
Differential Effects of Mitochondrial Heat Shock Protein 60 and Related Molecular Chaperones to Prevent Intracellular beta-Amyloid-induced Inhibition of Complex IV and Limit Apoptosis
J. Biol. Chem.,
October 6, 2006;
281(40):
29468 - 29478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Rosen, V. Veereshwarayya, C. E-H. Moussa, Q. Fu, M. S. Goldberg, M. G. Schlossmacher, J. Shen, and H. W. Querfurth
Parkin Protects against Mitochondrial Toxins and beta-Amyloid Accumulation in Skeletal Muscle Cells
J. Biol. Chem.,
May 5, 2006;
281(18):
12809 - 12816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Link, V. Fonte, B. Hiester, J. Yerg, J. Ferguson, S. Csontos, M. A. Silverman, and G. H. Stein
Conversion of Green Fluorescent Protein into a Toxic, Aggregation-prone Protein by C-terminal Addition of a Short Peptide
J. Biol. Chem.,
January 20, 2006;
281(3):
1808 - 1816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Oddo, A. Caccamo, I. F. Smith, K. N. Green, and F. M. LaFerla
A Dynamic Relationship between Intracellular and Extracellular Pools of A{beta}
Am. J. Pathol.,
January 1, 2006;
168(1):
184 - 194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Magrane, K. M. Rosen, R. C. Smith, K. Walsh, G. K. Gouras, and H. W. Querfurth
Intraneuronal {beta}-Amyloid Expression Downregulates the Akt Survival Pathway and Blunts the Stress Response
J. Neurosci.,
November 23, 2005;
25(47):
10960 - 10969.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Macario and E. C. de Macario
Sick Chaperones, Cellular Stress, and Disease
N. Engl. J. Med.,
October 6, 2005;
353(14):
1489 - 1501.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Christensen, A. Shtifman, P. D. Allen, J. R. Lopez, and H. W. Querfurth
Calcium Dyshomeostasis in {beta}-Amyloid and Tau-bearing Skeletal Myotubes
J. Biol. Chem.,
December 17, 2004;
279(51):
53524 - 53532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, N. Champagne, L. K. Beitel, C. G. Goodyer, M. Trifiro, and A. LeBlanc
Estrogen and Androgen Protection of Human Neurons against Intracellular Amyloid {beta}1-42 Toxicity through Heat Shock Protein 70
J. Neurosci.,
June 9, 2004;
24(23):
5315 - 5321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
