The Boron-Neuron Connection: The Potential of Boron-Containing Molecules for Treating Incurable Amyotrophic Lateral...

Boron (B), a group 13 metalloid, has emerged as a versatile element at the intersection of chemistry, biology, and medicine. Its electron-deficient nature and ability to reversibly interconvert between trigonal planar (sp²) and tetrahedral (sp³) geometries enable dynamic covalent interactions with biological nucleophiles, making boron-containing compounds (BCCs) attractive pharmacophores that selectively interact with reactive oxygen species (ROS) and are ROS-responsive for therapeutic development. BCCs possess antioxidant, anti-inflammatory, and metal-chelating properties that make them attractive candidates for neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS), a fatal and multifactorial motor neurodegenerative disorder, is characterized by oxidative stress, neuroinflammation, mitochondrial dysfunction, and metal dyshomeostasis, providing a strong rationale for exploring boron-based therapeutics.

This review examines current literature on B chemistry, pharmacology, and translational applications, with emphasis on mechanisms relevant to ALS pathogenesis. This review focuses on ROS-responsive B scaffolds, blood-brain barrier (BBB) permeability, neuroprotective mechanisms, hormonal modulation, metal chelation, and emerging preclinical evidence supporting boron-based interventions.

BCCs represent a promising yet underexplored therapeutic platform for ALS and related neurodegenerative disorders. Their ROS-responsive, redox-modulating, and neuroprotective properties, combined with favorable CNS drug-like pharmacokinetics, offer a mechanistically distinct approach to disease modification. Emerging preclinical evidence strongly supports further translational investigation.