Endogenous histidine peptides are physiological antioxidants that prevent oligodendrocyte cell death and myelin loss in vivo DOI

Clara Sajrawi,

Maali Odeh,

A. Tiwari

et al.

Glia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Abstract Histidine dipeptides (HDs) are synthesized in brain oligodendrocytes by carnosine synthase (carns1), but their role is unknown. Using metabolomics and vivo experiments with both constitutive oligodendrocyte‐selective carns1‐KO mouse models, we found that HDs critical for oligodendrocyte survival protect against oxidative stress. Carns1‐KO models had lower numbers of mature oligodendrocytes, increased lipid peroxidation, behavioral changes. Cuprizone administration, which increases reactive oxygen species vivo, resulted higher death, demyelination, axonal alterations, damage the corpus callosum mice. Gliosis cuprizone were prevented pretreatment antioxidant N‐acetylcysteine. NADPH levels threefold brains mice as an response to stress through acceleration pentose phosphate pathway (PPP). This was due overexpression glucose‐6‐phosphate dehydrogenase, rate‐limiting enzyme PPP. Likewise, expression NAD kinase, biosynthetic NADP+, NAMPT, replenishes NAD+ pool, than controls. Our observations suggest cell‐autonomously from stress, implications demyelinating diseases.

Language: Английский

Characterizing Oxidative Stress induced by Aβ Oligomers and the Protective Role of Carnosine in Primary Mixed Glia Cultures DOI Creative Commons
Vincenzo Cardaci, Lucia Di Pietro,

M. ZUPAN

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Altered expression of transfer RNAs and their possible roles in brain white matter injury DOI

Lingyi Huang,

Ding Bai, Xiaojuan Su

et al.

Neuroreport, Journal Year: 2024, Volume and Issue: 35(8), P. 536 - 541

Published: April 8, 2024

Transfer RNAs (tRNAs) can regulate cell behavior and are associated with neurological disorders. Here, we aimed to investigate the expression levels of tRNAs in oligodendrocyte precursor cells (OPCs) their possible roles regulation brain white matter injury (WMI). Newborn Sprague–Dawley rats (postnatal day 5) were used establish a model that mimicked neonatal WMI. RNA-array analysis was performed examine OPCs. psRNAtarget software predict target mRNAs significantly altered tRNAs. Gene ontology (GO) KEGG analyze pathways for mRNAs. Eighty-nine changed after WMI (fold change absolute ≥1.5, P < 0.01), 31 downregulated 58 upregulated. Among them, three identified, two being increased (chr10.trna1314-ProTGG chr2.trna2771-ProAGG) one decreased (chr10.trna11264-GlyTCC). Further, mRNA prediction GO/KEGG pathway indicated these mainly involved G-protein coupled receptor signaling beta-alanine metabolism, which both related myelin formation. In summary, OPCs WMI, suggesting may play important regulating This improves knowledge about pathophysiology provide novel treatment targets

Language: Английский

Citations

2
Histidine-containing dipeptide deficiency links to hyperactivity and depression-like behaviors in old female mice DOI

Jason Braga,

Takumi Komaru,

Mitsuki Umino

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 729, P. 150361 - 150361

Published: July 5, 2024

Language: Английский

Citations

1
Proteomics analysis of periplaque and chronic inactive multiple sclerosis lesions DOI Creative Commons

Jordan Wilkins,

Kiran K. Mangalaparthi,

Brian C. Netzel

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 21, 2024

Background Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by increased inflammation and immune responses, oxidative injury, mitochondrial dysfunction, iron dyshomeostasis leading to demyelination axonal damage. In MS, incomplete remyelination results in chronically demyelinated axons degeneration coinciding with disability. This suggests failure ability remyelinate however, precise underlying mechanisms remain unclear. We aimed identify proteins whose expression was altered chronic inactive white matter lesions periplaque MS tissue reveal potential pathophysiological mechanisms. Methods Laser capture microdissection coupled proteomics used interrogate spatially changes formalin-fixed paraffin-embedded brain from three individuals controls no apparent neurological complications. Histopathological maps guided lesions, matter, cortex along corresponding control tissue. Label free quantitation liquid chromatography tandem mass spectrometry discover differentially expressed between various regions. Results addition confirming loss several myelin-associated known be affected analysis revealed alterations myelin assembly, metabolism, cytoskeletal organization. The top compared consisted PPP1R14A, ERMN, SIRT2, CARNS1, MBLAC2. Conclusion Our findings highlight proteome which may crucial for proper myelinogenesis, bioenergetics, focal adhesions, cellular function. study highlights importance feasibility spatial approaches such as laser microdissection-based pathologically distinct regions Identification resolved should aid understanding development novel therapies.

Language: Английский

Citations

1
A comprehensive review on physiological and biological activities of carnosine: turning from preclinical facts to potential clinical applications DOI
Akshita Kumar, Geetha Suryakumar, Som Nath Singh

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

Language: Английский

Citations

0
Endogenous histidine peptides are physiological antioxidants that prevent oligodendrocyte cell death and myelin loss in vivo DOI

Clara Sajrawi,

Maali Odeh,

A. Tiwari

et al.

Glia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Abstract Histidine dipeptides (HDs) are synthesized in brain oligodendrocytes by carnosine synthase (carns1), but their role is unknown. Using metabolomics and vivo experiments with both constitutive oligodendrocyte‐selective carns1‐KO mouse models, we found that HDs critical for oligodendrocyte survival protect against oxidative stress. Carns1‐KO models had lower numbers of mature oligodendrocytes, increased lipid peroxidation, behavioral changes. Cuprizone administration, which increases reactive oxygen species vivo, resulted higher death, demyelination, axonal alterations, damage the corpus callosum mice. Gliosis cuprizone were prevented pretreatment antioxidant N‐acetylcysteine. NADPH levels threefold brains mice as an response to stress through acceleration pentose phosphate pathway (PPP). This was due overexpression glucose‐6‐phosphate dehydrogenase, rate‐limiting enzyme PPP. Likewise, expression NAD kinase, biosynthetic NADP+, NAMPT, replenishes NAD+ pool, than controls. Our observations suggest cell‐autonomously from stress, implications demyelinating diseases.

Language: Английский

Citations

0