Silence of resident microglia in GPI anchorless prion disease and activation of microglia in Gerstmann-Sträussler-Scheinker disease and sporadic Creutzfeldt-Jakob disease

Noguchi, Hideko; Koyama, Sachiko; Yagita, Kaoru; Shijo, Masahiro; Matsuzono, Kosuke; Hamasaki, Hideomi; Kanemaru, Takaaki; Okamoto, Tsukasa; Kai, Keita; Aishima, Shinichi; Abe, Kōji; Sasagasako, Naokazu; Honda, Hiroki

doi:10.1093/jnen/nlac098

Cited by 2 publications

(2 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even in sCJD, microglial activation depends on the type of PrPSc [18]. Microglia activation was also observed in GSS cases [19] and after prion infection [11,20]. This distinction emphasizes the complex nature of brain degeneration in prion diseases, indicating unique immune response mechanisms in different prion diseases.…”

Section: Glia Activationmentioning

confidence: 89%

Interactions between Cytokines and the Pathogenesis of Prion Diseases: Insights and Implications

Assis-de-Lemos,

Moura-do-Nascimento,

Amaral-do-Nascimento

et al. 2024

Brain Sciences

View full text Add to dashboard Cite

Transmissible Spongiform Encephalopathies (TSEs), including prion diseases such as Bovine Spongiform Encephalopathy (Mad Cow Disease) and variant Creutzfeldt–Jakob Disease, pose unique challenges to the scientific and medical communities due to their infectious nature, neurodegenerative effects, and the absence of a cure. Central to the progression of TSEs is the conversion of the normal cellular prion protein (PrPC) into its infectious scrapie form (PrPSc), leading to neurodegeneration through a complex interplay involving the immune system. This review elucidates the current understanding of the immune response in prion diseases, emphasizing the dual role of the immune system in both propagating and mitigating the disease through mechanisms such as glial activation, cytokine release, and blood–brain barrier dynamics. We highlight the differential cytokine profiles associated with various prion strains and stages of disease, pointing towards the potential for cytokines as biomarkers and therapeutic targets. Immunomodulatory strategies are discussed as promising avenues for mitigating neuroinflammation and delaying disease progression. This comprehensive examination of the immune response in TSEs not only advances our understanding of these enigmatic diseases but also sheds light on broader neuroinflammatory processes, offering hope for future therapeutic interventions.

show abstract

Section: Glia Activationmentioning

confidence: 89%

Interactions between Cytokines and the Pathogenesis of Prion Diseases: Insights and Implications

Assis-de-Lemos,

Moura-do-Nascimento,

Amaral-do-Nascimento

et al. 2024

Brain Sciences

View full text Add to dashboard Cite

show abstract

“…We performed immunoelectron microscopy with in situ nanogold labeling in immunohistochemistry on paraffin sections [ 27 , 28 ] to investigate the ultrastructure of PrP depositions. Routine immunohistochemical staining with anti‐PrP primary antibody (3F4) and DAB on the paraffin sections were briefly performed, and micrographs were obtained.…”

Section: Methodsmentioning

confidence: 99%

Altered properties of amyloidogenic prion protein in genetic Creutzfeldt–Jakob disease with PRNP V180I mutation in response to pentosan polysulfate

Shijo

Yoshimura

Omae³

et al. 2023

Brain Pathology

Self Cite

View full text Add to dashboard Cite

Genetic Creutzfeldt–Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease‐resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease‐resistant PrP deposition. It has been suggested that PPS might reduce protease‐resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease‐resistant PrP using both a conventional procedure and size‐exclusion gel chromatography for the purification of oligomeric PrP. Both PPS‐treated cases showed long survival time over 5 years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1‐year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4‐expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non‐PPS cases revealed protease‐resistant PrP in the oligomeric fraction only, whereas the PPS‐treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP‐oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP‐oligomer.

show abstract

Silence of resident microglia in GPI anchorless prion disease and activation of microglia in Gerstmann-Sträussler-Scheinker disease and sporadic Creutzfeldt-Jakob disease

Cited by 2 publications

References 33 publications

Interactions between Cytokines and the Pathogenesis of Prion Diseases: Insights and Implications

Interactions between Cytokines and the Pathogenesis of Prion Diseases: Insights and Implications

Altered properties of amyloidogenic prion protein in genetic Creutzfeldt–Jakob disease with PRNP V180I mutation in response to pentosan polysulfate

Contact Info

Product

Resources

About