The insulin receptor (INSR), a heterotetrameric receptor tyrosine kinase (RTK), consists of two extracellular α subunits and two transmembrane β subunits interconnected by disulfide bonds. The α subunits facilitate high-affinity insulin binding, while the β subunits harbor an intracellular tyrosine kinase domain critical for signal transduction. Ligand binding induces conformational changes, prompting β subunit autophosphorylation at specific tyrosine residues (e.g., Y1158, Y1162), which activates the kinase and initiates downstream signaling cascades such as the IRS/PI3K/AKT and Ras/MAPK pathways. These pathways regulate glucose homeostasis, lipid metabolism, and cell proliferation. INSR is predominantly expressed in metabolic tissues-liver, skeletal muscle, and adipose-where it mediates insulin's anabolic effects, including GLUT4-mediated glucose uptake, glycogen synthesis, and suppression of hepatic gluconeogenesis. Its expression in non-metabolic tissues (e.g., kidneys, immune cells, and fibroblasts) implicates broader roles in neuronal survival, immune modulation, and tissue repair. Dysregulation of INSR signaling underpins pathologies like type II diabetes, characterized by insulin resistance due to impaired receptor activation or trafficking. Conversely, aberrant INSR hyperactivity is associated with cancer progression via sustained pro-survival and mitogenic signaling. Structural and functional studies highlight INSR's dual role as a metabolic regulator and growth promoter, making it a pivotal therapeutic target for metabolic disorders and oncology.
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.