Targeting Aβ25-35-Induced Neuronal Senescence-Like Features Using Curcumin-Loaded Solid Self-Emulsifying Drug...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Curcumin exhibits anti-neurodegenerative properties but suffers from poor solubility and bioavailability.
• Curcumin-loaded Solid Self-Emulsifying Drug Delivery Systems (C-SSEDDS) were developed to enhance curcumin's pharmacokinetic profile and neuronal targeting.
• The precise molecular mechanisms of curcumin in Alzheimer's Disease (AD)-related neuronal senescence are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of C-SSEDDS in targeting neuronal senescence-like features in an in vitro Alzheimer's Disease model.
• To evaluate the therapeutic potential of C-SSEDDS in counteracting amyloid-beta (Aβ)-induced neuronal damage and senescence.

Main Methods:

• An in vitro model of neuronal senescence was induced in SK-N-SH cells using Aβ25-35.
• Cells were treated with optimized concentrations of C-SSEDDS or commercial curcumin.
• Assessed cell viability, morphology, SA-β-gal activity, ROS levels, and expression of NLRP3, Sirt-1, and synaptophysin.

Main Results:

• C-SSEDDS significantly improved cell viability and reduced apoptosis and SA-β-gal positive cells in Aβ25-35-treated cells.
• C-SSEDDS decreased intracellular ROS and NLRP3 expression while upregulating Sirt-1 and synaptophysin.
• C-SSEDDS demonstrated superior efficacy compared to commercial curcumin and was comparable to N-acetylcysteine (NAC).

Conclusions:

• C-SSEDDS effectively counteracts Aβ25-35-induced neuronal damage and senescence-like features in vitro.
• The formulation mitigates oxidative stress, inflammation, and apoptosis, while enhancing Sirt-1 activity and synaptic plasticity.
• C-SSEDDS shows promise as a therapeutic strategy for Alzheimer's Disease-related neuronal dysfunction.