Seashells by the zinc shore: a meeting report of the International Society for Zinc Biology, Asilomar, CA 2014

The 2014 ISZB meeting provided an exciting forum for presenting zinc biology-related research across the full spectrum. ISZB meetings are among the few scientific gatherings that are truly interdisciplinary, bringing together scientists from widely diverging fields, all having in common the desire to study the role of zinc in biological systems. Thus membrane transporters and cell signaling are discussed with relevance to structure/ function relationships, while physiological and pathophysiological studies are described in many species and across most organ systems. Novel tools and techniques are presented to researchers and potential users to allow dissemination of zinc research-related information for the benefit of a wide scientific community studying various aspects of zinc in biology. This is one meeting that should not be missed by biochemists, cell and molecular biologists, physiologists, or anyone interested in the rich and exciting biology of zinc. We all look forward to our next gathering in Istanbul, Turkey, September 25-29, 2016, http://iszb2016turkey.medicine.Ankara.edu.tr. The ISZB would like to thank Qiagen, Pfizer, Teva Pharmaceutical Industries, Novartis Pharma AG, Shino Test Corporation, Strem Chemicals, Genostaff and Hamari Chemicals for their generous donations that helped support the meeting. Book prizes for excellent talks were kindly provided by The Royal Society of Chemistry, Springer and IOS Press. Travel awards were supported in part by NIH grant GM112419. The authors would also like to thank Wolfgang Maret, Daren L. Knoell, Robert A. Colvin and David I. Soybel for their invaluable contributions to the organization of the meeting

Visually driven modulation of glutamatergic synaptic transmission is mediated by the regulation of intracellular polyamines

Ca2+-permeable AMPARs are inwardly rectifying due to block by intracellular polyamines. Neuronal activity regulates polyamine synthesis, yet whether this affects Ca2+-AMPAR-mediated synaptic transmission is unknown. We test whether 4 hr of increased visual stimulation regulates glutamatergic retino-tectal synapses in Xenopus tadpoles. Tectal neurons containing Ca2+-AMPARs form a gradient along the rostro-caudal developmental axis. These neurons had inwardly rectifying AMPAR-mediated EPSCs. Four hours of visual stimulation or addition of intracellular spermine increased rectification in immature neurons. Polyamine synthesis inhibitors blocked the effect of visual stimulation, suggesting that visual activity regulates AMPARs via the polyamine synthesis pathway. This modulation resulted in changes in the integrative properties of tectal neurons. Regulation of polyamine synthesis by physiological stimuli is a novel form of modulation of synaptic transmission important for understanding the short-term effects of enhanced sensory experience during development

Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection

Achieving neuroprotection in ischemic stroke patients has been a multidecade medical challenge. Numerous clinical trials were discontinued in futility and many were terminated in response to deleterious treatment effects. Recently, however, several positive reports have generated the much-needed excitement surrounding stroke therapy. In this review, we describe the clinical studies that significantly expanded the time window of eligibility for patients to receive mechanical endovascular thrombectomy. We further summarize the results available thus far for nerinetide, a promising neuroprotective agent for stroke treatment. Lastly, we reflect upon aspects of these impactful trials in our own studies targeting the Kv2.1-mediated cell death pathway in neurons for neuroprotection. We argue that recent changes in the clinical landscape should be adapted by preclinical research in order to continue progressing toward the development of efficacious neuroprotective therapies for ischemic stroke

The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction.

Zinc is a highly abundant cation in the brain, essential for cellular functions, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential (MMP), leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and excitotoxic calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting

The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction.

Zinc is a highly abundant cation in the brain, essential for cellular functions, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential (MMP), leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and excitotoxic calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting