Plant-Derived Exosome-Like Nanoparticles in Neurodegenerative Diseases: From Dual Bioactive-Delivery Roles to...

Area of Science:

• Nanomedicine
• Neuroscience
• Pharmacology

Background:

• Neurodegenerative diseases, including Alzheimer's disease (AD), are challenging to treat due to complex pathogenesis and limited drug delivery to the central nervous system (CNS).
• Plant-derived exosome-like nanoparticles (PELNs) are natural nanovesicles with inherent bioactivity and carrier properties, offering potential for neuroprotection and improved drug delivery.

Purpose of the Study:

• To review the dual role of PELNs as bioactive agents and delivery systems for AD and related neurodegenerative disorders.
• To explore the mechanisms by which PELNs may exert neuroprotective effects and overcome delivery barriers.
• To examine advancements in PELN isolation, characterization, and engineering for therapeutic applications.

Main Methods:

• Literature review focusing on the mechanisms of action, delivery capabilities, and translational challenges of PELNs in neurodegenerative disease models.
• Analysis of studies investigating PELN interactions with neuroinflammatory pathways, protein aggregation, and the gut-brain axis.
• Evaluation of current methods for PELN isolation, purification, cargo loading, and surface modification.

Main Results:

• PELNs demonstrate potential in modulating neuroinflammation, redox balance, mitochondrial function, protein aggregation, and neural repair.
• Their composition allows for gastrointestinal stability, systemic transport, and potential blood-brain barrier (BBB) penetration.
• Advances in engineering PELNs enhance their stability, targeting, and loading capacity.

Conclusions:

• PELNs offer a promising platform for neurodegenerative disease therapeutics, combining intrinsic bioactivity with nanocarrier advantages.
• Overcoming challenges related to heterogeneity, standardization, quality control, and biosafety is crucial for clinical development.
• Establishing robust Chemistry, Manufacturing, and Controls (CMC) frameworks and translational pathways is essential to advance PELNs into clinical practice.