The presence of senile plaques containing abundant amyloid-beta (Abeta) peptide is one of the major pathological hallmarks of Alzheimer's disease (AD). Recent studies support the notion that overexpression of zinc transporters (ZnT) is involved in zinc metabolic disturbances and Abeta aggregation in AD brains. Here we present data showing an elevated expression of zinc transporter 3 (ZnT3) protein, revealed by immunoblotting assay, in the cerebellum of the amyloid-beta protein precursor (AbetaPP)/presenilin 1 (PS1) transgenic mouse. Confocal microscopic and autometallographic results showed that ZnT3 immunofluorescence and zinc ions were predominantly located in the amyloid plaques. ZnT3 protein was abundantly distributed throughout the plaques, whereas zinc ions were mainly located in the peripheral parts of rosette-shaped plaques with a lightly stained center. Collectively, our results suggest that ZnT3 protein is involved in the Abeta aggregation in the cerebellum of the AbetaPP/PS1 mouse.
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http://dx.doi.org/10.3233/JAD-2010-1363 | DOI Listing |
J Neurosci
January 2025
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Morgantown, WV, USA.
Synaptically released zinc is a neuronal signaling system that arises from the actions of the presynaptic vesicular zinc transporter protein ZnT3. Mechanisms that regulate the actions of zinc at synapses are of great importance for many aspects of synaptic signaling in the brain. Here, we identify the astrocytic zinc transporter protein ZIP12 as a candidate mechanism that contributes to zinc clearance at cortical synapses.
View Article and Find Full Text PDFFront Cell Neurosci
October 2024
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Disruption of inhibitory interneurons is common in the epileptic brain and is hypothesized to play a pivotal role in epileptogenesis. Abrupt disruption and loss of interneurons is well-characterized in status epilepticus models of epilepsy, however, status epilepticus is a relatively rare cause of epilepsy in humans. How interneuron disruption evolves in other forms of epilepsy is less clear.
View Article and Find Full Text PDFFEBS Lett
January 2025
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Zinc transporters (ZnTs) act as H/Zn antiporters, crucial for zinc homeostasis. Brain-specific ZnT3 expressed in synaptic vesicles transports Zn from the cytosol into vesicles and is essential for neurotransmission, with ZnT3 dysfunction associated with neurological disorders. Ubiquitously expressed ZnT4 localized to lysosomes facilitates the Zn efflux from the cytosol to lysosomes, mitigating the cell injury risk.
View Article and Find Full Text PDFJ Neurochem
October 2024
Laboratory of Neurobiology, Max-Planck-Institute for Biophysical Chemistry and University of Göttingen, Göttinge, Germany.
The heterotrimeric G-protein αo subunit is ubiquitously expressed in the CNS as two splice variants Gα and Gα, regulating various brain functions. Here, we investigated the effect of single Gα, Gα, and double Gα knockout on the postnatal development of the murine mossy fiber tract, a central pathway of the hippocampal connectivity circuit. The size of the hippocampal synaptic termination fields covered by mossy fiber boutons together with various fiber length parameters of the tract was analyzed by immunohistochemical staining of the vesicular Zinc transporter 3 (ZnT3) or Synaptoporin at postnatal days 2, 4, 8, 12, 16, and in the adult.
View Article and Find Full Text PDFEMBO Rep
November 2024
Shanghai Stomatological Hospital, School of Stomatology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.
Zinc transporter 1 (ZnT1), the principal carrier of cytosolic zinc to the extracellular milieu, is important for cellular zinc homeostasis and resistance to zinc toxicity. Despite recent advancements in the structural characterization of various zinc transporters, the mechanism by which ZnTs-mediated Zn translocation is coupled with H or Ca remains unclear. To visualize the transport dynamics, we determined the cryo-electron microscopy (cryo-EM) structures of human ZnT1 at different functional states.
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