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Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2

Russell, Claire L ; Semerdjieva, Sophia ; Empson, Ruth M ; Austen, Brian M ; Beesley, Philip W ; Alifragis, Pavlos Ferreira, Sergio T.

PloS one, 2012-08, Vol.7 (8), p.e43201 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2
Autor: Russell, Claire L ; Semerdjieva, Sophia ; Empson, Ruth M ; Austen, Brian M ; Beesley, Philip W ; Alifragis, Pavlos
Ferreira, Sergio T.
Assuntos: Alzheimer Disease - metabolism ; Alzheimer's disease ; Amyloid beta-Peptides - biosynthesis ; Animal cognition ; Animals ; Biology ; Brain ; Brain slice preparation ; CHO Cells ; Cricetinae ; Data processing ; Dementia ; Dementia disorders ; Electrophysiology ; Electrophysiology - methods ; Exocytosis ; Hippocampus ; Hippocampus - embryology ; Hippocampus - metabolism ; Immunoglobulins ; Labeling ; Localization ; Medicine ; Neurodegeneration ; Neurons ; Neurons - metabolism ; Neurosciences ; Neurotransmitter Agents - metabolism ; Neurotransmitter release ; Oligomers ; Peptides - chemistry ; Proteins ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission ; Synaptophysin ; Synaptophysin - metabolism ; Translocation ; Vesicle-Associated Membrane Protein 2 - metabolism ; β-Amyloid
É parte de: PloS one, 2012-08, Vol.7 (8), p.e43201
Notas: Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: PA RME. Performed the experiments: CLR SS. Analyzed the data: CLR SS RME PA. Contributed reagents/materials/analysis tools: PA PWB BMA. Wrote the paper: PA.
Descrição: It is becoming increasingly evident that deficits in the cortex and hippocampus at early stages of dementia in Alzheimer's disease (AD) are associated with synaptic damage caused by oligomers of the toxic amyloid-β peptide (Aβ42). However, the underlying molecular and cellular mechanisms behind these deficits are not fully understood. Here we provide evidence of a mechanism by which Aβ42 affects synaptic transmission regulating neurotransmitter release. We first showed that application of 50 nM Aβ42 in cultured neurones is followed by its internalisation and translocation to synaptic contacts. Interestingly, our results demonstrate that with time, Aβ42 can be detected at the presynaptic terminals where it interacts with Synaptophysin. Furthermore, data from dissociated hippocampal neurons as well as biochemical data provide evidence that Aβ42 disrupts the complex formed between Synaptophysin and VAMP2 increasing the amount of primed vesicles and exocytosis. Finally, electrophysiology recordings in brain slices confirmed that Aβ42 affects baseline transmission. Our observations provide a necessary and timely insight into cellular mechanisms that underlie the initial pathological events that lead to synaptic dysfunction in Alzheimer's disease. Our results demonstrate a new mechanism by which Aβ42 affects synaptic activity.
Editor: United States: Public Library of Science
Idioma: Inglês

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Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2

Russell, Claire L ; Semerdjieva, Sophia ; Empson, Ruth M ; Austen, Brian M ; Beesley, Philip W ; Alifragis, Pavlos Ferreira, Sergio T.

United States: Public Library of Science

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