Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Language：English   Publisher：FEBS Open Bio  

Alzheimer's disease (AD) is the most common cause of dementia. A genome-wide association study has shown that several AD risk genes are involved in lipid metabolism. Additionally, epidemiological studies have indicated that the levels of several lipid species are altered in the AD brain. Therefore, lipid metabolism is likely changed in the AD brain, and these alterations might be associated with an exacerbation of AD pathology. Oligodendrocytes are glial cells that produce the myelin sheath, which is a lipid-rich insulator. Dysfunctions of the myelin sheath have been linked to white matter abnormalities observed in the AD brain. Here, we review the lipid composition and metabolism in the brain and myelin and the association between lipidic alterations and AD pathology. We also present the abnormalities in oligodendrocyte lineage cells and white matter observed in AD. Additionally, we discuss metabolic disorders, including obesity, as AD risk factors and the effects of obesity and dietary intake of lipids on the brain.

DOI： 10.1002/2211-5463.13661

Web of Science

Scopus

PubMed

Language：English   Publisher：Neurobiology of Disease  

Organelle contact sites are multifunctional platforms for maintaining cellular homeostasis. Alternations of the mitochondria-associated membranes (MAM), one of the organelle contact sites where the endoplasmic reticulum (ER) is tethered to the mitochondria, have been involved in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the detailed mechanisms through which MAM integrity is disrupted in ALS have not been fully elucidated. Here, we examined whether AAA ATPase domain-containing protein 3A (ATAD3A), a mitochondrial membrane AAA ATPase accumulating at the MAM, is involved in ALS. We found that sigma-1 receptor (σ1R), an ER-resident MAM protein causative for inherited juvenile ALS, required ATAD3A to maintain the MAM. In addition, σ1R retained ATAD3A as a monomer, which is associated with an inhibition of mitochondrial fragmentation. ATAD3A dimerization and mitochondrial fragmentation were significantly induced in σ1R-deficient or SOD1-linked ALS mouse spinal cords. Overall, these observations indicate that MAM induction by σ1R depends on ATAD3A and that σ1R maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation. Our findings suggest that targeting σ1R–ATAD3A axis would be promising for a novel therapeutic strategy to treat mitochondrial dysfunction in neurological disorders, including ALS.

DOI： 10.1016/j.nbd.2023.106031

Web of Science

Scopus

PubMed

Language：English   Publisher：Center for Academic Publications Japan  

<p>We previously demonstrated that ascorbic acid (AsA) deficiency, caused by an AsA-free diet, induces inflammatory changes in the liver and intestine of osteogenic disorder Shionogi (ODS) rats that cannot synthesize AsA. However, whether low AsA intake induces inflammatory changes remains unknown. Here, we assessed the inflammatory changes in ODS rats caused by low AsA intake and compared them to ODS rats that were fed a diet supplemented with sufficient amounts of AsA (300 mg/kg). Male ODS rats (12-wk-old) were fed an AsA-free diet (0 ppm group), AsA 20 mg/kg diet (20 ppm group), AsA 40 mg/kg diet (40 ppm group) or AsA 300 mg/kg diet (300 ppm group) for 22 d. The hepatic mRNA levels of acute phase proteins, including C-reactive protein (CRP) and haptoglobin, were higher in the 0 and 20 ppm groups, than in the 300 and 40 ppm groups, but were not significantly higher in the 20 ppm group. Serum CRP concentrations were significantly higher in the 0 and 20 ppm groups than in the 300 and 40 ppm groups. Jejunal and ileal interleukin-1β (IL-1β) mRNA levels were higher in the 0 and 20 ppm groups than in the 300 ppm group. Jejunal and ileal IL-6 mRNA levels tended to be higher in the 0 and 20 ppm groups than in the 300 ppm group. Furthermore, the portal IL-6 concentration gradually increased with decrease in the AsA intake. Thus, inflammatory changes could occur in both AsA-deficient ODS rats and ODS rats with low AsA intake.</p>

DOI： 10.3177/jnsv.68.481

Scopus

PubMed

CiNii Research

Language：Japanese   Publisher：公益社団法人 日本ビタミン学会  

DOI： 10.20632/vso.95.3_81

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Responsible for pages：768-773   Language：Japanese

Event date： 2023.8

Language：English   Presentation type：Poster presentation  

Event date： 2023.5

Language：Japanese   Presentation type：Poster presentation  

Venue：札幌  

Event date： 2022.11

Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

Event date： 2022.6

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2022.6

Language：English   Presentation type：Poster presentation