Therapeutic Effect of Padina arborescens Extract on a Cell System Model for Parkinson's Disease

Area of Science:

• Neuroscience
• Pharmacology
• Marine Biology

Background:

• Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are key players in Parkinson's disease (PD) pathogenesis.
• LRRK2 activity in microglia drives neuroinflammation, while α-synuclein induces oxidative stress and neuroinflammation.
• Inhibiting LRRK2 is a therapeutic strategy for neuroinflammatory responses in PD.

Purpose of the Study:

• To investigate the neuroprotective effects of the marine alga Padina arborescens extract.
• To examine the extract's impact on LRRK2 activation, α-synuclein aggregation, and neuroinflammation.
• To evaluate the potential of P. arborescens as a therapeutic agent for PD.

Main Methods:

• In vitro assays using BV2 microglial cells, primary rat microglia, primary rat astrocytes, and recombinant α-synuclein.
• Inhibition of LRRK2 activity and α-synuclein fibrillization.
• Assessment of inflammatory markers (TNF-α, iNOS, nitric oxide) and oxidative stress.
• Cellular assays in differentiated human dopaminergic neuronal cell line SH-SY5Y (dSH) and lifespan studies in Caenorhabditis elegans.

Main Results:

• P. arborescens extract inhibited LRRK2 activity and LPS-induced LRRK2 upregulation in BV2 cells.
• The extract attenuated pro-inflammatory mediators (TNF-α, iNOS, nitric oxide) in microglial cells.
• It prevented rotenone-induced oxidative stress in astrocytes and inhibited α-synuclein fibrillization in vitro and in neuronal cells.
• Increased lysosomal activity in dSH cells and prolonged lifespan in C. elegans treated with rotenone.

Conclusions:

• Padina arborescens extract demonstrates significant anti-neuroinflammatory and anti-aggregation properties.
• The extract effectively modulates LRRK2 activity and α-synuclein pathology, key mechanisms in Parkinson's disease.
• P. arborescens shows therapeutic potential for Parkinson's disease by mitigating neuroinflammation and oxidative stress.