An Open Question: Is the A2A Adenosine Receptor a Novel Target for Alzheimer’s Disease Treatment?

Alzheimer’s disease (AD) is one of the most common neurodegenerative pathologies. Its incidence is in dramatic growth in Western societies and there is a need of both biomarkers to support the clinical diagnosis and drugs for the treatment of AD. The diagnostic criteria of AD are based on clinical data. However, it is necessary to develop biomarkers considering the neuropathology of AD. The A2A receptor, a G-protein coupled member of the P1 family of adenosine receptors, has different functions crucial for neurodegeneration. Its activation in the hippocampal region regulates synaptic plasticity and in particular glutamate release, NMDA receptor activation and calcium influx. Additionally, it exerts effects in neuroinflammation, regulating the secretion of pro-inflammatory cytokines. In AD patients, its expression is increased in the hippocampus/entorhinal cortex more than in the frontal cortex, a phenomenon not observed in age-matched control brains, indicating an association with AD pathology. It is upregulated in peripheral blood cells of patients affected by AD, thus reflecting its increase at central neuronal level. This review offers an overview on the main AD biomarkers and the potential role of A2A adenosine receptor as a new marker and therapeutic target.

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Huprine Y – tryptophan heterodimers with potential implication to Alzheimer’s disease treatment

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2021.128100 ◽

2021 ◽

pp. 128100

Author(s):

Eva Mezeiova ◽

Martina Hrabinova ◽

Vendula Hepnarova ◽

Daniel Jun ◽

Jana Janockova ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Treatment ◽

Potential Implication

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In silico and in vitro anti-AChE activity investigations of constituents from Mytragyna speciosa for Alzheimer’s disease treatment

Journal of Computer-Aided Molecular Design ◽

10.1007/s10822-020-00372-4 ◽

2021 ◽

Author(s):

Wansiri Innok ◽

Asadhawut Hiranrat ◽

Netnapa Chana ◽

Thanyada Rungrotmongkol ◽

Panita Kongsune

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

In Silico ◽

Ache Activity ◽

Disease Treatment

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The Neuronal Actions of Leptin and the Implications for Treating Alzheimer’s Disease

Pharmaceuticals ◽

10.3390/ph14010052 ◽

2021 ◽

Vol 14 (1) ◽

pp. 52

Author(s):

Kirsty Hamilton ◽

Jenni Harvey

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Energy Homeostasis ◽

Leptin Receptor ◽

Hippocampal Formation ◽

Synaptic Function ◽

Receptor Expression ◽

Neuroprotective Actions ◽

Novel Target ◽

Leptin System

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.

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