{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Guanine deaminase (GDA), an enzyme that catalyzes the deamination of guanine into xanthine, plays multifaceted roles in both peripheral and neural tissues. In addition to its canonical function in purine degradation and homeostasis—as evidenced by its tissue‐specific distribution in liver, kidney, and intestine"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and its application in reducing purine levels in food products"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "—GDA has emerged as a key regulator in neural development and function. In the central nervous system, an alternatively spliced form of GDA, known as cypin, promotes dendritic branching via modulation of microtubule assembly"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", thus shaping neuronal architecture and synaptic connectivity. Small molecule activators of cypin’s deaminase activity have even been shown to protect neurons against excitotoxic injury and improve functional recovery after brain trauma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", although studies in non‐mammalian models indicate that GDA functionality and its influence on microtubule dynamics may be species specific."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the skin, GDA contributes to photoageing and pigmentation. Upregulation of GDA in keratinocytes following ultraviolet exposure increases reactive oxygen species and DNA damage, thereby accelerating cellular senescence in conditions such as seborrheic keratosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while its enhanced expression in epidermal keratinocytes also appears to stimulate melanogenesis through the upregulation of key factors including stem cell factor and endothelin-1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, genetic linkage studies have associated the genomic region near the GDA locus with psychiatric outcomes; for instance, a common single-nucleotide polymorphism downstream of the GDA gene has been linked to increased suicidal ideation during antidepressant treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Additional studies in motor neurons also suggest that GDA expression may confer neuroprotection, contributing to differential vulnerability among motor neuron subpopulations"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and elevations in serum GDA activity have been observed in inflammatory conditions such as ankylosing spondyloarthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the dual roles of GDA in metabolic regulation and the modulation of cellular morphology. Whether by influencing purine degradation pathways in peripheral tissues or by shaping dendritic architecture and synaptic efficiency in the brain, GDA represents a critical enzymatic node whose dysregulation may contribute to diverse pathophysiological states ranging from neurodegeneration and psychiatric disorders to cutaneous photoageing and pigmentary abnormalities.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kenichiro Kubo, Hirohito Honda, Hirohito Honda, et al. 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