Related Experiment Video
Updated: Mar 30, 2026
09:36
Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
7.1K
Adenosine A2A Receptors Modulate α-Synuclein Aggregation and Toxicity
Diana G Ferreira1,2,3,4, Vânia L Batalha1, Hugo Vicente Miranda1
1Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa.
Cerebral Cortex (New York, N.Y. : 1991)
|November 5, 2015
Summary
Adenosine A2A receptor antagonists protect against Parkinson's disease by reducing alpha-synuclein inclusions. This neuroprotection involves NMDA receptor mechanisms, offering a potential therapeutic target for synucleinopathies.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Alpha-synuclein (aSyn) aggregation is central to Parkinson's disease (PD) and related synucleinopathies.
- Adenosine A2A receptor (A2AR) antagonists show promise for PD treatment, but their mechanisms are not fully understood.
Purpose of the Study:
- To investigate the neuroprotective mechanisms of A2AR blockade against aSyn-induced neurotoxicity.
- To assess the impact of A2AR antagonism on synaptic plasticity and cell death.
Main Methods:
- Utilized A2AR knockout (KO) mice and selective A2AR antagonists.
- Assessed long-term potentiation (LTP) impairment and neuronal cell death in response to aSyn oligomers.
- Examined aSyn aggregation and inclusion formation in cell models (SH-SY5Y) and primary neuronal cultures.
Main Results:
- A2AR blockade or deletion rescued aSyn-induced LTP impairment via NMDA receptor-dependent pathways.
- A2AR antagonists prevented cell death induced by aSyn oligomers.
- A2AR antagonists reduced aSyn inclusions without affecting initial oligomerization.
Conclusions:
- A2AR antagonists may exert neuroprotection by modulating later stages of aSyn aggregation, reducing toxic inclusions.
- A2AR represents a viable therapeutic target for Parkinson's disease and other synucleinopathies.
Related Concept Videos
01:31Adrenergic Receptors: ɑ Subtype
3.2K
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
3.2K
01:29Drugs Affecting Neurotransmitter Synthesis
2.5K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
2.5K
01:21Drugs Affecting Neurotransmitter Release or Uptake
1.8K
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
1.8K
01:17Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
1.8K
Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
1.8K
01:22Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
1.8K
α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
1.8K
01:26Adrenergic Receptors: β Subtype
4.4K
β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
4.4K