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Differentiated Alzheimer's disease transmitochondrial cybrid cell lines exhibit reduced organelle movement
Author(s): Trimmer PA, Borland MK
Source: ANTIOXIDANTS & REDOX SIGNALING    Volume: 7    Issue: 9-10    Pages: 1101-1109    Published: SEP-OCT 2005  
Times Cited: 21     References: 57     
Abstract: The axonal transport and function of organelles like mitochondria and lysosomes may be impaired and play an important role in the pathogenesis of Alzheimer's disease (AD). Unique cybrid cell lines that model AD pathology were created by fusing platelets containing mitochondria from age-matched AD and control volunteers with mitochondrial DNA-free SH-SY5Y human neuroblastoma cells. These cybrid lines were differentiated to form process-bearing neuronal cells. Mitochondria and lysosomes in the neurites of each cybrid line were fluorescently labeled to determine the kinetics of organelle movement. The mitochondria in AD cybrid neurites were elongate, whereas the mitochondria in control cybrid neurites were short and more punctate. The mean velocity of mitochondrial movement, as well as the percentage of moving mitochondria, was significantly reduced in AD cybrids. The velocity of lysosomal movement was also reduced in the processes of AD cybrid cells, suggesting that the axonal transport machinery may be compromised in cybrid cell lines that contain mitochondrial DNA derived from AD patients. Reduced mitochondrial and lysosomal movement in susceptible neurons may compromise function in metabolically demanding structures like synaptic terminals and participate in the terminal degeneration that is characteristic of AD.
Document Type: Article
Language: English
Reprint Address: Trimmer, PA (reprint author), Univ Virginia, Dept Neurol, POB 800394,Hosp Dr, Charlottesville, VA 22908 USA
Addresses:
1. Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA
Publisher: MARY ANN LIEBERT INC, 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
Subject Category: Biochemistry & Molecular Biology; Endocrinology & Metabolism
IDS Number: 958VR
ISSN: 1523-0864
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