Related Experiment Videos
Insight into the mechanism of laquinimod action
1Department of Neuropathology, University Medical Center, Georg-August University, Göttingen, Germany. wbrueck@med.uni-goettingen.de
Journal of the Neurological Sciences
|March 25, 2011
Summary
Laquinimod, an oral medication, effectively reduced brain lesions and inflammation in multiple sclerosis (MS) patients. It also minimized nerve damage and modulated immune responses in preclinical models.
Area of Science:
- Neuroimmunology
- Pharmacology
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS).
- Current treatments for MS aim to reduce inflammation and slow disease progression.
Purpose of the Study:
- To evaluate the efficacy and tolerability of laquinimod in patients with multiple sclerosis.
- To investigate the mechanism of action of laquinimod in preclinical models of MS.
Main Methods:
- Clinical trial assessing gadolinium-enhancing lesions in MS patients treated with oral laquinimod.
- Preclinical studies using experimental autoimmune encephalomyelitis (EAE) models in mice to assess inflammation, demyelination, and axonal damage.
- In vitro analysis of cytokine profiles from peripheral blood mononuclear cells (PBMCs).
Main Results:
- Laquinimod significantly reduced gadolinium-enhancing lesions in MS patients.
- Oral laquinimod reached the CNS in healthy and EAE mice.
- Laquinimod inhibited acute and chronic EAE, minimizing inflammation, demyelination, and axonal damage.
- In vitro, laquinimod modulated pro- and anti-inflammatory cytokine production.
- Laquinimod treatment increased serum brain-derived neurotrophic factor (BDNF) levels.
Conclusions:
- Laquinimod is a well-tolerated oral therapy effective in reducing CNS inflammation, demyelination, and axonal damage in MS.
- Laquinimod demonstrates neuroprotective effects and modulates immune responses, offering a potential therapeutic strategy for multiple sclerosis.
Related Concept Videos
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
01:21Antiprotozoal Agents
Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
01:23Local Anesthetics: Mechanism of Action
Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
01:28Depolarizing Blockers: Mechanism of Action
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine...
01:17Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...