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„Ÿ ƒLate Breaking Symposium\2„V‚ฝ‚ศŽแ”Nซ”F’mวF_ŒoŽฒ๕ƒWƒXƒgƒƒtƒB[‚๐”บ‚คˆโ“`ซ”’Žฟ”]วiHDLSj „Ÿ

ˆโ“`ซ”’Žฟ”]ว‚ฦhereditary diffuse leukoencephalopathy with spheroidsiHDLSj‚ฬ•ชŽq•a‘ิ

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VŠƒ‘ๅŠw’ดˆๆŠwp‰@E_Œo“เ‰ศkง951\8585 VŠƒŽs’†‰›‹ๆˆฎ’ฌ’ส1\757l

Adult-onset leukoencephalopathy involving the white matter of the brain is a heterogeneous disorder that exhibits a wide range of clinical manifestations. Recent advances in molecular genetics enable gene-based diagnosis of some forms of adult-onset leukoencephalopathy. In this review, the classification of adult-onset leukoencephalopathy based on molecular genetic findings is proposed. The autosomal dominant forms of adult-onset leukoencephalopathy include hereditary diffuse leukoencephalopathy with spheroids (HDLS), autosomal dominant adultonset leukoencephalopathy (ALDL), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Alexander disease. The autosomal recessive forms of adult-onset leukoencephalopathy include cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), vanishing white matter (VWM) with leukoencephalopathy, Nasu-Hakola disease, and metachromatic leukodystrophy (MDL). X-chromosome-linked disorders include fragile X-associated tremor and ataxia syndrome (FXTAS) and adrenoleukodystrophy (ALD). Identification of the genes responsible for adult-onset leukoencephalopathy provides an important clue for elucidation of molecular pathophysiology underlying white matter disorders. One example is the identification of mutations in colony stimulating factor 1 receptor (CSF-1R) in patients with HDLS. Missense and splice site mutations have been found in the tyrosine kinase domain of CSF-1R. CSF-1R is highly expressed in microglia in the brain. It has been demonstrated that mice depleted of CSF-1R exhibit loss of microglia in the brain. In addition, stimulation of IL-34, a ligand of CSF-1R, induces proliferation and activation of microglia. These findings raise an intriguing possibility that dysfunction of microglia may play a role in the pathogenesis of white matter lesions occurring in patients with HDLS.
(—ีฐ_Œo, 52F1386|1389, 2012)
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(Ž๓•t“๚F2012”N5ŒŽ25“๚)

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