The Boron–Neuron Connection: The Potential of Boron‐Containing Molecules for Treating Incurable Amyotrophic Lateral Sclerosis

Background: 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 ( sp ² ) and tetrahedral ( sp ³ ) 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.

Methods: 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.

Conclusions: 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.