N-acetyl-L-leucine (NALL), a stereospecific derivative of the essential amino acid L-leucine, has attracted increasing attention as a candidate therapy for neurological disorders. Preclinical and clinical studies suggest both symptomatic and neuroprotective effects. This review summarizes evidence on the mechanisms of action, preclinical findings, and clinical outcomes of NALL, and discusses its therapeutic prospects in neurological health and disease. A structured literature search of PubMed, Scopus, and Google Scholar was conducted to identify preclinical and clinical studies evaluating N-acetyl-L-leucine (NALL) in neurological disorders. Preclinical studies demonstrated that NALL enhances mitochondrial bioenergetics, reduces oxidative stress, restores lysosomal and autophagic function, and modulates neuroinflammation. In rodent models, NALL improved motor coordination, neuronal survival, and recovery following traumatic brain injury. Clinical trials in Niemann-Pick disease type C and GM2 gangliosidoses showed improvements in motor function, quality of life, and disease progression, with sustained benefit during extension phases. Preliminary evidence also suggests possible roles in multiple sclerosis, ataxia telangiectasia, Parkinson’s disease, and multiple sulfatase deficiency. NALL was consistently well tolerated with a favorable safety profile. NALL shows multimodal mechanisms and promising translational potential for both rare and common neurological disorders. While early evidence is encouraging, larger randomized trials are required to confirm efficacy, define optimal dosing, and determine its place in neurological therapeutics.
Abid et al. (Thu,) studied this question.