Table of Contents

Reviews

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  • Yuhong Chen,
  • Matthew Bedell,
  • and Kang Zhang

  Age-related Macular Degeneration: Genetic and Environmental Factors of Disease

  Mol Interv October 2010 10:271-281; doi:10.1124/mi.10.5.4
  • Abstract
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  Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as the population ages. Unfortunately, treatment options remain limited because the etiology and pathogenesis of AMD are incompletely defined. Recently, gene association and mechanistic studies have confirmed that AMD involves the interaction of multiple genetic and environmental factors. The identification of genes that have a substantial impact on the risk for AMD is not only facilitating the diagnosis and screening of populations at risk, but is also elucidating key molecular pathways of pathogenesis. In this way, modern research into AMD exemplifies the power of pharmacogenetic studies, not only with respect to the dawning of personalized medicine, but also in terms of refining our molecular understanding of disease.

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  • Luke A. D. Bury and
  • Shasta L. Sabo

  How It’s Made: The Synapse

  Mol Interv October 2010 10:282-292; doi:10.1124/mi.10.5.5
  • Abstract
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  Most of the synapses that appear in the developing central nervous system (CNS) are formed en passant, meaning they occur along the length of the extending axon, and not merely at the axon terminus. The construction of CNS synapses thus ensues from the temporal and spatial coordination of contacts between growing neurons, and this coordination is predicated on the formation of subcellular structures in each of the neurons that contribute to synapse formation. This review focuses on the proteins and vesicular processes that corroborate in the formation of presynaptic terminals. Understanding the delivery of vesicular cargo to the developing synapse, along with elucidation of the interplay among protein and membrane components at the nascent synapse, is relevant for treating brain diseases as diverse as autism, epilepsy, anxiety disorders, brain injury, and Alzheimer’s disease.

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  • Anika M.S. Hartz and
  • Björn Bauer

  Regulation of ABC Transporters at the Blood-Brain Barrier: New Targets for CNS Therapy

  Mol Interv October 2010 10:293-304; doi:10.1124/mi.10.5.6
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  Recognition of the blood–brain barrier (BBB) can be traced back to the late nineteenth century, when Paul Ehrlich observed that intravenously administered water-soluble dyes failed to enter the central nervous system (CNS). Still today, the BBB poses major pharmacological challenges, for example, in the development of effective CNS drugs and the exploitation of certain imaging technologies. It has furthermore become clear that certain pathophysiological processes, such as the inadequate clearance of amyoloid species in Alzheimer’s disease, may directly reflect BBB functionality. A critical component of the BBB is a group of ATP-binding cassette (ABC) efflux transporters that act to protect the brain from xenobiotics, and a number of therapeutic avenues that would inhibit, activate, or otherwise exploit these ABC proteins have been envisaged. This review highlights a novel strategy––targeting signaling pathways that control ABC transporters at the BBB––for the development of CNS therapies.

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  • Pierre J. Marie

  Strontium Ranelate in Osteoporosis and Beyond: Identifying Molecular Targets in Bone Cell Biology

  Mol Interv October 2010 10:305-312; doi:10.1124/mi.10.5.7
  • Abstract
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  Osteoporosis is characterized by reduced bone mass and the deterioration of bone microarchitecture, resulting in bone fragility and increased susceptibility to fractures. Whereas the majority of antiosteoporotic therapies have depended on either antiresorptive drugs or anabolic hormone treatment, a novel mode of action appears to be mediated by strontium ranelate, which has been shown to act both by opposing bone resorption and promoting bone formation in vitro. This review article addresses the cellular and molecular mechanisms that have been implicated in the therapeutic strengthening of bone observed upon administration of strontium ranelate to osteoporotic patients. These mechanisms relate to specific pathways of calcium signaling, including complex networks involving nuclear factor of activated T cells (NFAT) and Wnt signaling.