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Novel crosstalk mechanisms between GluA3 and Epac2 in synaptic plasticity and memory in Alzheimer's disease.
Zhang, Tong; Dolga, Amalia M; Eisel, Ulrich L M; Schmidt, Martina.
Afiliación
  • Zhang T; Department of Molecular Pharmacology, University of Groningen, the Netherlands; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen 9747 AG, Netherlands.
  • Dolga AM; Department of Molecular Pharmacology, University of Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Eisel ULM; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen 9747 AG, Netherlands.
  • Schmidt M; Department of Molecular Pharmacology, University of Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: m.schmidt@rug.nl.
Neurobiol Dis ; 191: 106389, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38142840
ABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disease which accounts for the most cases of dementia worldwide. Impaired memory, including acquisition, consolidation, and retrieval, is one of the hallmarks in AD. At the cellular level, dysregulated synaptic plasticity partly due to reduced long-term potentiation (LTP) and enhanced long-term depression (LTD) underlies the memory deficits in AD. GluA3 containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are one of key receptors involved in rapid neurotransmission and synaptic plasticity. Recent studies revealed a novel form of GluA3 involved in neuronal plasticity that is dependent on cyclic adenosine monophosphate (cAMP), rather than N-methyl-d-aspartate (NMDA). However, this cAMP-dependent GluA3 pathway is specifically and significantly impaired by amyloid beta (Aß), a pathological marker of AD. cAMP is a key second messenger that plays an important role in modulating memory and synaptic plasticity. We previously reported that exchange protein directly activated by cAMP 2 (Epac2), acting as a main cAMP effector, plays a specific and time-limited role in memory retrieval. From electrophysiological perspective, Epac2 facilities the maintenance of LTP, a cellular event closely associated with memory retrieval. Additionally, Epac2 was found to be involved in the GluA3-mediated plasticity. In this review, we comprehensively summarize current knowledge regarding the specific roles of GluA3 and Epac2 in synaptic plasticity and memory, and their potential association with AD.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Neurobiol Dis Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Neurobiol Dis Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos