Bariatric surgery and subsequent weight loss lead to a reversal of peripheral blood monocytosis in obesity.

In 1885, the German physician Friedrich Pelizaeus first described a familial disorder mainly characterized by nystagmus, developmental delay, spastic paraplegia, and ataxia []. Subsequently, in 1910, Ludwig Merzbacher confirmed the X-linked recessive inheritance pattern of the disease [], which was later named Pelizaeus–Merzbacher disease. In this review, we first summarize the molecular regulators governing PLP biosynthesis, trafficking, and myelin assembly, then discuss how distinct PLP1 mutations disrupt ER proteostasis and activate maladaptive UPR signaling, ultimately leading to oligodendrocyte (OL) dysfunction and demyelination. Finally, we highlight emerging therapeutic strategies targeting proteostasis restoration and ER stress modulation. The neuropathological features of PMD are primarily characterized by widespread hypomyelination and white matter atrophy within the central nervous system, accompanied by astrocytic proliferation and subcortical axonal degeneration, with surviving axons frequently showing spherical swelling []. Macroscopically, cerebral atrophy is most evident as thinning of the corpus callosum, although the telencephalon and cerebellum are also commonly affected. Microscopically, neuronal loss is observed in multiple brain regions, particularly in the cerebellum, with frequent involvement of the hippocampus, substantia nigra-striatum, and thalamus. Together, the affected white matter contains morphologically heterogeneous “myelin islands,” the distribution of which correlates with disease severity: patients with severe forms exhibit an almost complete absence of white matter myelination, whereas those with milder forms display characteristic “tigroid-like” changes in the central white matter []. Histochemical staining further demonstrates abundant small neutral lipid droplets dispersed throughout the astrocytic cytoplasm, suggesting that PMD may be associated with abnormalities in myelin lipoproteins or related lipid metabolism. In the spinal cord, pathological involvement is relatively mild in the thalamocerebellar and anterior spinocerebellar tracts, whereas marked myelin abnormalities are observed in the corticospinal, dorsal, dorsolateral, and dorsal spinocerebellar tracts [].