β-Alanine Is an Unexploited Neurotransmitter in the Pathogenesis and Treatment of Alzheimer's Disease

Alzheimer's disease (AD) remains an unmet medical challenge, as there are no effective therapies that alter the disease's progression. While approaches have targeted molecules like acetylcholine (ACh) and glutamate, these strategies have provided only limited benefits and do not address the complex molecular mechanisms underlying AD development. This review suggests that β-alanine (3-aminopropanoic acid) is an underexplored neurotransmitter that could serve as a potential AD drug target. Existing evidence indicates that β-alanine modulates GABAergic and glutamatergic neurotransmission, thereby affecting neuronal hyperexcitability. Additionally, studies suggest that β-alanine has antioxidant effects, reducing oxidative stress caused by reactive oxygen species (ROS). We propose that β-alanine might bind to Aβ/tau proteins, possibly targeting the six-amino acid sequences EVHHQK/DDKKAK, which are involved in protein aggregation. β-Alanine may also influence the release of pro-inflammatory cytokines from microglia, potentially reducing neuroinflammation. We also hypothesize that β-alanine may help regulate metal dyshomeostasis, which leads to ROS production. Taurine, structurally like β-alanine, appears to influence comparable mechanisms. Although structural similarity doesn't ensure therapeutic effectiveness, this evidence supports considering β-alanine as a treatment for AD. Furthermore, β-alanine and its analogues face challenges, including crossing the blood-brain barrier (BBB) and optimizing structure-activity relationships (SAR). This review includes articles through September 2025, sourced from four databases.