Role of amyloid β protein receptors in mediating synaptic plasticity

Abstract

Abstract. There are few diseases in modern biomedicine that have garnered as much scientific interest and public concern as Alzheimer's disease (AD). The amyloid hypothesis has become the dominant model of AD pathogenesis; however, the details of the hypothesis are changing over time. Recently, given the increasing recognition, subtle effects of amyloid β protein (Aβ) on synaptic efficacy may be critical to AD progression. Synaptic plasticity is the important neurochemical foundation of learning and memory. Recent studies have identified that soluble Aβ oligomers combine with certain receptors to impair synaptic plasticity in AD, which advanced the amyloid hypothesis. The aim of the present review was to summarize the role of Aβ-relevant receptors in regulating synaptic plasticity and their downstream signaling cascades, which may provide novel insights into the understanding of the pathogenesis of AD and the development of therapeutic strategies to slow down the progression of AD-associated memory decline in the early stages.

Early compensatory responses against neuronal injury: A new therapeutic window of opportunity for Alzheimer's Disease?

“…To date, oA β is acknowledged as the most synaptotoxic aggregate . oA β specifically interacts with a variety of receptors on the surface of both neuronal and glial cells, evoking signaling cascades that in turn modify the cellular profile of gene transcription/protein expression . In general, research on A β toxicity has focused mainly on its detrimental effects, culminating with significant declines in synaptic activity, neuronal metabolism, neurotrophic factors, as well as increased glial activation/inflammation.…”

“…4,5 oAβ specifically interacts with a variety of receptors on the surface of both neuronal and glial cells, evoking signaling cascades that in turn modify the cellular profile of gene transcription/protein expression. [6][7][8][9] In general, research on Aβ toxicity has focused mainly on its detrimental effects, culminating with significant declines in synaptic activity, neuronal metabolism, neurotrophic factors, as well as increased glial activation/inflammation. However, a more attentive look at the literature of the last two decades, points out the existence of a biphasic trend where all these reductions are preceded by transient paradoxical rises.…”

Withaferin A Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine Associated Neurological Dysfunctions

“…Aβ peptides then aggregate into extracellular insoluble senile plaques (Echeverria et al, 2004 ; Guardia-Laguarta et al, 2010 ; Ahyayauch et al, 2012 ). This Aβ accumulation leads to decreased neuronal health and stability, increased deterioration, synaptic depression (Venkitaramani et al, 2007 ; Palop and Mucke, 2010 ; Li et al, 2017 ), oxidative stress (Butterfield et al, 2013 ; Arimon et al, 2015 ; Cheignon et al, 2018 ), augmented neuronal dysfunctions and inflammation (Barage and Sonawane, 2015 ; Marottoli et al, 2017 ). These dysfunctions caused by Aβ aggregation, become worst upon the presence of HIV-1 (András and Toborek, 2013 ; Martínez-Bonet et al, 2018 ) and drugs of abuse.…”

DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission and reducing neuronal loss

“…Increasing evidence has demonstrated that the progressive loss of synapses is an important characteristic of AD. Synapses are the sites of memory storage in the nervous system and the mechanism by which information is transferred, suggesting a relationship between synaptic plasticity degeneration and cognitive decline in AD [ 6 , 7 ]. Long-term potentiation (LTP) has been widely used for evaluating synaptic plasticity both in vitro and in vivo.…”