Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Department of Pathology and Experimental Therapeutics, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, 08907 Barcelona, L'Hospitalet de Llobregat, Spain.
Int J Mol Sci. 2022 Jun 6;23(11):6341. doi: 10.3390/ijms23116341.
Primary microglial leukodystrophy or leukoencephalopathy are disorders in which a genetic defect linked to microglia causes cerebral white matter damage. Pigmented orthochromatic leukodystrophy, adult-onset orthochromatic leukodystrophy associated with pigmented macrophages, hereditary diffuse leukoencephalopathy with (axonal) spheroids, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) are different terms apparently used to designate the same disease. However, ALSP linked to dominantly inherited mutations in (colony stimulating factor receptor 1) cause CSF-1R-related leukoencephalopathy (CRP). Yet, recessive ALSP with ovarian failure linked to (alanyl-transfer (t)RNA synthase 2) mutations (LKENP) is a mitochondrial disease and not a primary microglial leukoencephalopathy. Polycystic membranous lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; Nasu-Hakola disease: NHD) is a systemic disease affecting bones, cerebral white matter, selected grey nuclei, and adipose tissue The disease is caused by mutations of one of the two genes or , identified as PLOSL1 and PLOSL2, respectively. TYROBP associates with receptors expressed in NK cells, B and T lymphocytes, dendritic cells, monocytes, macrophages, and microglia. encodes the protein TREM2 (triggering receptor expressed on myeloid cells 2), which forms a receptor signalling complex with TYROBP in macrophages and dendritic cells. Rather than pure microglial leukoencephalopathy, NHD can be considered a multisystemic "immunological" disease.
原发性小胶质细胞脑白质营养不良或脑白质病是一种遗传性疾病，与小胶质细胞有关的基因缺陷导致脑白质损伤。色素性正染性脑白质营养不良、伴色素性巨噬细胞的成人型正染性脑白质病、遗传性弥漫性脑白质病伴（轴索）球体、伴轴索球体和色素性神经胶质的成人型脑白质病（ALSP）是不同的术语，显然用于指定同一种疾病。然而，与显性遗传突变相关的 ALSP （集落刺激因子受体 1）导致 CSF-1R 相关脑白质病（CRP）。然而，与卵巢衰竭相关的隐性 ALSP 与 （丙氨酰转移（t）RNA 合成酶 2）突变（LKENP）相关，是一种线粒体疾病，而不是原发性小胶质细胞脑白质病。多囊膜性脂膜性骨发育不良伴硬化性脑白质病（PLOSL；Nasu-Hakola 病：NHD）是一种影响骨骼、脑白质、选定的灰质核和脂肪组织的系统性疾病。该疾病由两个基因之一的突变引起，分别鉴定为 PLOSL1 和 PLOSL2。TYROBP 与 NK 细胞、B 和 T 淋巴细胞、树突状细胞、单核细胞、巨噬细胞和小胶质细胞中表达的受体结合。编码蛋白 TREM2（髓样细胞触发受体 2），它在巨噬细胞和树突状细胞中与 TYROBP 形成受体信号复合物。NHD 不能被认为是一种纯粹的小胶质细胞脑白质病，而可以被认为是一种多系统的“免疫”疾病。
