Table of Contents

December 2003; 3 (8)

Crosstalk

  • The Personal and Professional: Of One Mind

    Mol Interv December 2003 3:430-435; doi:10.1124/mi.3.8.430

Viewpoints

    • Sergio Fazio and
    • MacRae F. Linton

    Apolipoprotein AI as Therapy for Atherosclerosis: Does the Future of Preventive Cardiology Include Weekly Injections of the HDL Protein?

    Mol Interv December 2003 3:436-440; doi:10.1124/mi.3.8.436

    Conventional wisdom suggests that halting or reversing long-term atherosclerosis requires increasing the amount of circulating high-density lipoprotein (HDL) coursing through the vasculature. However, recent evidence seems to indicate that reducing the size of cholesterol-containing lipid plaques might be accomplished by methods that either do not raise or, in fact, lower the amount of circulating HDL. Carriers of apoAIMilano, a variant of apoprotein AI (a component of HDL), have reduced levels of circulating low-density lipoprotein (LDL). Intriguingly, these individuals have reduced amounts of circulating HDL and total apoAI. Infusions of the ApoAIMilano variant given to patients with coronary atherosclerosis appear to lead to disease regression and reduced plaque size. However, larger studies are required to provide definitive proof of apoAIMilano’s benefits. What is certain is that attention should be focused on the removal of cholesterol from plaques rather than simply desiring to raise HDL concentrations in patients.

    • Rosanne M. Thomas and
    • Daniel A. Peterson

    A Neurogenic Theory of Depression Gains Momentum

    Mol Interv December 2003 3:441-444; doi:10.1124/mi.3.8.441

    The rate of adult neurogenesis fluctuates in response to several environmental factors. Chronic stress, which can lead to neuronal apoptosis and dendritic atrophy, certainly affects the overall rate of neurogenesis in the adult brain. Depression, which arises from several causes, including chronically stressful situations, is known to correlate with altered hippocampal morphology. But is the link between depression and neuronal regeneration merely coincidental? Recent studies indicate that ingestion of antidepressants leads to increased neurogenesis in the hippocampus. However, the hippocampus is generally thought important for learning and memory—not for “mood” state—thus, there is much more to the story that requires clarification. Also, caveats abound in the interpretation of neurogenesis in the amelioration of depression; nonetheless, these results are quite intriguing and might point to better design and prediction of new-generation antidepressants.

Reviews

    • Robert Hnasko and
    • Michael P. Lisanti

    The Biology of Caveolae: Lessons from Caveolin Knockout Mice and Implications for Human Disease

    Mol Interv December 2003 3:445-464; doi:10.1124/mi.3.8.445

    Caveolae are microdomains of the cell membranes of diverse cell types. The presence of caveolins within these microdomains is definitive of caveolae, and attempts to understand the roles of these proteins in cell-cycle regulation, membrane trafficking, and cell signaling rely on gene knockout technologies. As has been the case for many protein families, deletion of multiple caveolins, despite their obvious importance, results in viable and healthy mice. The molecular characterization of knockout tissues, however, explains the potential for caveolin-null mice to develop a wide variety of progressive diseases, provided that the animals are exposed to risk factors. Knockout animals that are deficient in caveolin, in fact, may provide animal models for a vast array of human diseases, ranging from cancer and diabetes to muscular dystrophy and urogenital disease. Careful physiological analysis, moreover, continues to delineate the roles of the caveolins in several aspects of basic cell biology.

    • Stefanie N. Vogel,
    • Katherine A. Fitzgerald,
    • and Matthew J. Fenton

    TLRs: Differential Adapter Utilization by Toll-Like Receptors Mediates TLR-Specific Patterns of Gene Expression

    Mol Interv December 2003 3:466-477; doi:10.1124/mi.3.8.466

    Much research goes into identifying just how large families of receptors can elicit quite specific (and in many cases, quite distinct) profiles of gene expression. Differing combinations of receptor subunits certainly abet specificity, as does the distinct recruitment of particular cytoplasmic signaling proteins, including catalytically inactive adapter proteins. Unfortunately, different labs observe different results, depending on cells, conditions, and methodologies used, so that a number of conflicting reports exist with regard to which adapter protein binds to which receptors, and whether interactions are direct or bridged by additional proteins. The expanding field of Toll-like receptor (TLR) research has been hampered by such inconsistencies; however, close examination of the primary research reveals which interactions are likely to be most relevant.

Net Results

  • Sites of interest on the World Wide Web–edited by Rick Neubig

    Mol Interv December 2003 3:478; doi:10.1124/mi.3.8.478

Beyond the Bench

Outliers

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This Issue

December 2003; 3 (8)
Cover
  1. Crosstalk
  2. Viewpoints
  3. Reviews
  4. Net Results
  5. Beyond the Bench
  6. Outliers

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