The leptin receptor (LEPR), a class I cytokine receptor transmembrane protein, is encoded by the LEPR gene located on chromosome 1p31. Structurally, it comprises an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular signaling region. Alternative splicing generates multiple isoforms, with the long isoform (LEPR-b) containing the full intracellular domain essential for JAK-STAT signaling activation, while shorter isoforms (LEPR-a/c/d/f) exhibit truncated cytoplasmic tails with distinct regulatory roles. The mature protein consists of 1165 amino acids (≈132.4 kDa) and exists in both membrane-bound and soluble forms (LEPR-e)[1]. Functionally, LEPR mediates leptin's effects on energy homeostasis through hypothalamic POMC/AgRP neurons, suppressing appetite while enhancing energy expenditure via brown adipose thermogenesis and skeletal muscle fatty acid oxidation. Peripherally, it modulates hepatic gluconeogenesis, adipogenesis, and adipose tissue autocrine signaling. Isoform-specific expression patterns are observed: LEPR-a predominates in adult heart, liver, and reproductive organs, whereas LEPR-b is enriched in thalamus and skeletal muscle. NK cells co-express both isoforms, suggesting immune-metabolic crosstalk. Genetic alterations in LEPR correlate with metabolic dysregulation, including hyperleptinemia, insulin resistance, and obesity. Its complex spatiotemporal expression and isoform diversity underscore its pleiotropic roles in systemic metabolic integration.
Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ.