Journal
JOURNAL OF NEUROCHEMISTRY
Volume 110, Issue 4, Pages 1254-1262Publisher
WILEY
DOI: 10.1111/j.1471-4159.2009.06222.x
Keywords
Alzheimer's disease; apolipoprotein E; lipoprotein; neuroprotective; transforming growth factor-beta
Categories
Funding
- NIH [NS40994, AG23708]
- John Douglas French Alzheimer's Foundation (IT) and the Alzheimer's Association (IT)
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Transforming growth factor-beta 1 (TGF-beta 1) has central functions in development, tissue maintenance, and repair and has been implicated in major diseases. We discovered that TGF-beta 1 contains several amphipathic helices and hydrophobic domains similar to apolipoprotein E (apoE), a protein involved in lipoprotein metabolism. Indeed, TGF-beta 1 associates with lipoproteins isolated from human plasma, cultured liver cells, or astrocytes, and its bioactivity was highest in high-density lipoprotein preparations. Importantly, lipoproteins containing the apoE3 isoform had higher TGF-beta levels and bioactivity than those containing apoE4, a major genetic risk factor for atherosclerosis and Alzheimer's disease. Because TGF-beta 1 can be protective in these diseases an association with apoE3 may be beneficial. Association of TGF-beta with different types of lipoproteins may facilitate its diffusion, regulate signaling, and offer additional specificity for this important growth factor.
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