This review synthesizes mechanisms and translational strategies for controlled blood–brain barrier modulation (e.g., receptor-mediated transcytosis, ligand-engineered nanocarriers, focused ultrasound, viral/molecular engineering) to improve delivery of neuroprotective, anti-α-synuclein, and…

By detailing clinically actionable BBB delivery platforms, safety considerations, and biomarker-directed approaches, the paper addresses a key translational bottleneck for Parkinson’s therapeutics—enabling targeted brain delivery of α-synuclein-targeting and neuroprotective agents that could…

The blood-brain barrier (BBB) plays an indispensable role in central nervous system homeostasis but it has remained a key barrier to successful treatment of neurodegenerative and demyelinating diseases. This review discusses the basis for BBB structural and functional regulation and critically discusses emerging strategies to improve therapeutic delivery in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Across pharmacological, nanotechnological, physical and genetic platforms, comes a common thread of ideas; rational and temporally-controlled BBB modulation is the uniting theme that underlies effective and safe brain-targeted therapy. Approaches such as receptor-mediated transcytosis, ligand-engineered nanocartiers, focused ultrasound with microbubbles, osmotic disruption, and electroporation or molecular or viral engineering have expanded the therapeutic landscape, but potential translational application relies upon reversibility, spatial selection, and preservation of neurovascular integrity. The discipline is shifting past proof-of-concept research to clinically-incrementally actionable paradigms anchored on pharmacokinetic accuracy, biomarker-directed goal involvement, and safety strict examination. The growing body of evidence has implied that bio-modulation of the BBB can augment the delivery of neuroprotective, anti-amyloid, anti-a-synuclein, and remyelinating therapeutic treatment with minimal systemic exposure and off-target damage. Together, BBB modulation is transitioning to become an experimental strategy of delivery, but with great clinical potential as a precision therapeutic strategy.