RAPGEF4

Last update 08 May 2025

Basic Info

Synonyms

exchange protein directly activated by cAMP 2, cAMP-GEFII, cAMP-regulated guanine nucleotide exchange factor II

+ [9]

Introduction

Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarity).

100 Clinical Results associated with RAPGEF4

100 Translational Medicine associated with RAPGEF4

0 Patents (Medical) associated with RAPGEF4

369

Literatures (Medical) associated with RAPGEF4

01 Nov 2025·Neural Regeneration Research

Targeting Epac2 and GluA3-containing AMPARs: a novel therapeutic strategy for Alzheimer’s disease

Article

Author: Schmidt, Martina ; Zhang, Tong

Alzheimer′s disease (AD) is a neurodegenerative disease that manifests progressive decline in memory and cognition.In the early stage of AD, memory retrieval is impaired preceding memory acquisition and consolidation (Roy et al., 2016).Prior to the onset of symptoms, pathol. amyloid-β (Aβ) plagues and tau protein tangles accumulate in extracellular and intracellular spaces, resp., leading to neurodegeneration.Among these hallmark pathologies, Aβ is proposed to be the primary etiol. by triggering a cascade of pathogenic events, including neuroinflammation, oxidative stress, tau hyperphosphorylation, synaptic/neuronal dysfunction, and neuronal death (Zhang et al., 2023b).

01 Aug 2025·Neuropharmacology

Activation of Epac2 improves Aβ-induced impairment of memory retrieval in an acute model of Alzheimer's disease

Article

Author: Chameau, Pascal ; Kessels, Helmut W ; Chen, Tingting ; Schmidt, Martina ; Eisel, Ulrich L M ; Marmolejo-Garza, Alejandro ; Douwenga, Wanda ; Zhang, Tong ; Zhang, Yuequ ; Dolga, Amalia M

Impaired memory retrieval is one of the cognitive markers in the early stage of Alzheimer's Disease (AD). Previous studies report that exchange protein directly activated by cAMP 2 (Epac2) plays a specific and time-limited role in promoting memory retrieval. In this study, we investigated the effect of a novel Epac2 activator, S220, on neuronal and synaptic activities, and memory impairment in an acute AD mouse model. S220 treatment increased the firing rate of action potential and intracellular calcium in primary neurons. Moreover, S220 treatment increased synaptic currents in CA1 neurons. In the acute AD mouse model, intrahippocampal injection of amyloid-β (Aβ) oligomers impaired memory performance. Notably, administering S220 20 minutes before retention of contextual fear conditioning recovered the Aβ-induced memory impairment, suggesting an enhancing effect on memory retrieval. Collectively, our data demonstrate that the novel Epac2 activator S220 promotes synaptic communication and neuronal firing, and thereby improves Aβ-induced memory impairment via enhancing memory retrieval, indicating the role of Epac2 as a potential treatment target for AD.

01 Mar 2025·Neuropsychopharmacology

Epac2 activation drives calcium permeable-AMPA receptor accumulation, fueling the incubation of cocaine craving

Article

Author: Ma, Yao-Ying ; Guo, Changyong

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RAPGEF4

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