Decreased levels of PDI and P5 in oligodendrocytes in Alzheimer's disease. Issue 6 (21st July 2017)

• Record Type: Journal Article
• Authors: Honjo, Yasuyuki; Ayaki, Takashi; Tomiyama, Takami; Horibe, Tomohisa; Ito, Hidefumi; Mori, Hiroshi; Takahashi, Ryosuke; Kawakami, Koji
• Is Part Of: Neuropathology. Volume 37:Issue 6(2017:Dec.)
• Page Start: 495
• Page End: 501
• Publication Date: 2017-07-21
• Subjects: Alzheimer's disease -- oligodendrocyte -- P5‐protein disulfide isomerase -- protein disulfide isomerase -- S‐nitrosylation; Nervous system -- Diseases -- Periodicals; Nervous system -- Pathophysiology -- Periodicals; 616.8047
• DOI: 10.1111/neup.12395
• Languages: English
• ISSNs: 0919-6544

Abstract

Abstract: Protein disulfide isomerase (PDI) is a chaperone protein located in the endoplasmic reticulum (ER). Nitric oxide‐induced S‐nitrosylation of PDI inhibits its enzymatic activity, leading to protein accumulation and activation of the unfolded protein response. Protein disulfide isomerase P5 (P5) is a member of the PDI family that mostly localizes to the ER lumen. Both S‐nitrosylated PDI and S‐nitrosylated P5 are found in Alzheimer's disease (AD) brain. Previously, we showed that expression of the ER stress marker, growth arrest, and DNA damage protein (GADD34) was significantly increased in neurons and oligodendrocytes in AD brain. In the present study, we showed that PDI and P5 levels were significantly decreased in oligodendrocytes in the brains of AD patients and an AD mouse model. Interestingly, these decreases were evident before the animals displayed typical AD pathology. Because we previously showed that small short interfering RNA knockdown of PDI or P5 could affect the viability of neuronal cells under ER stress, dysfunction of PDI and P5 under ER stress could cause apoptosis of neuronal cells. In summary, we showed that the levels of PDI and P5 were significantly decreased in the oligodendrocytes of AD patients. This phenomenon was also found in an AD mouse model before the animals displayed AD pathology. The overall findings suggest that oligodendrocytes may play important roles in AD pathogenesis.