Related Experiment Video

Updated: Jun 18, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
09:04

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

Published on: September 7, 2010

Toll-like receptor 2 is required for opioids-induced neuronal apoptosis

Yi Li1, Hui Li, Yi Zhang

  • 1Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.

Biochemical and Biophysical Research Communications
|November 17, 2009
PubMed

Insights

Opioids increase Toll-like receptor 2 (TLR2) expression in neurons, leading to cell death. Inhibiting TLR2 can prevent opioid-induced neuronal damage, offering a potential therapeutic target.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Pharmacology

Background:

  • Toll-like receptor 2 (TLR2) is crucial for immune responses and expressed in the nervous system.
  • Opioids are known to inhibit cell growth and induce apoptosis.
  • The mechanism of TLR2-mediated apoptosis by opioids remains unclear.

Purpose of the Study:

  • To elucidate the role of TLR2 in opioid-induced apoptosis in primary neurons.
  • To investigate the signaling pathway involved in TLR2-mediated neuronal apoptosis.

Main Methods:

  • Primary neurons were treated with morphine chronically.
  • TLR2 expression (mRNA and protein) was measured.
  • Apoptosis was assessed in wild-type and TLR2-deficient neurons.
  • Caspase-3 activation and GSK3beta phosphorylation were analyzed.

Main Results:

  • Chronic morphine treatment significantly upregulated TLR2 expression in primary neurons.
  • TLR2 deficiency markedly reduced morphine-induced apoptosis.
  • Caspase-3 activation and GSK3beta phosphorylation were impaired in TLR2-deficient neurons following morphine treatment.

Conclusions:

  • Opioids induce neuronal apoptosis by upregulating TLR2 expression.
  • TLR2 plays a critical role in mediating opioid-induced neuronal apoptosis via GSK3beta signaling.
  • Targeting TLR2 may prevent opioid-induced neurotoxicity.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.