CSF1R相关白质脑病:从遗传性弥漫性白质脑病合并轴索球样变到原发性小胶质细胞病

CSF1R-related leukoencephalopathy: from hereditary diffuse leukoencephalopathy with spheroids to primary microgliopathy

遗传性弥漫性白质脑病合并轴索球样变(HDLS)是一种罕见的常染色体显性遗传性白质脑病,以进行性神经精神症状和运动障碍为主要临床表现,女性比男性更早出现症状;影像学呈现弥漫性脑白质损害、胼胝体变薄、脑组织钙化灶等改变;病理学特征为原发性轴索变性及髓鞘缺失。集落刺激因子1受体(CSF1R)是目前唯一确定的HDLS致病基因,主要表达于小胶质细胞,因此CSF1R相关白质脑病被视为原发性小胶质细胞病的代表,小胶质细胞在该病的发病机制中发挥关键作用。了解CSF1R相关白质脑病研究现状与进展,有助于揭示小胶质细胞可能的病理生理学作用和未来研究方向。

Hereditary diffuse leukoencephalopathy with spheroids(HDLS)is a rare autosomal dominant hereditary leukoencephalopathy.Progressive neuropsychiatric symptoms and motor disorders are the main clinical manifestations,and women appear earlier than men.In imaging,diffusing white matter damage,thinning of the corpus callosum and brain calcification are characteristic changes.Primary axonal degeneration and absence of myelin sheath are characteristic histopathological changes.Colony stimulating factor 1 receptor(CSF1 R)is the only pathogenic gene of HDLS currently.Since CSF1 R is mainly expressed in microglia,CSF1 R-related leukoencephalopathy can be regarded as a representative of primary microgliopathy,and microglia play a key role in the pathogenesis of this disease.In this review,we discuss the current progress of CSF1 R-related leukoencephalopathy,and reveal the possible pathophysiological role of microglia,as well as future research directions.