Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12912 - 12912

Опубликована: Авг. 18, 2023

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play vital role in maintaining integrity myelin, protective sheath around nerve fibres essential for efficient signal transmission. However, MS, oligodendrocytes become dysfunctional, leading to myelin damage axonal degeneration. Emerging evidence suggests that metabolic changes, including mitochondrial dysfunction alterations glucose lipid metabolism, contribute significantly pathogenesis MS. Mitochondrial observed both immune cells within CNS MS patients. Impaired function leads energy deficits, affecting crucial processes such as impulse transmission transport, ultimately contributing Moreover, linked generation reactive oxygen species (ROS), exacerbating inflammation. Altered metabolism affects supply required oligodendrocyte synthesis. Dysregulated results changes composition its stability integrity. Importantly, low levels polyunsaturated fatty acids are associated with upregulated enhanced catabolism. Understanding intricate relationship between these mechanisms developing targeted therapies preserve promote neurological recovery individuals Addressing aspects may offer new insights into potential therapeutic strategies halt progression improve quality life

Язык: Английский

---

Reversible reduction in brain myelin content upon marathon running

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Here we use magnetic resonance imaging to study the impact of marathon running on brain structure in humans. We show that signal for myelin water fraction—a surrogate content—is substantially reduced upon specific regions involved motor coordination and sensory emotional integration, but recovers within two months. These findings suggest content is temporarily reversibly diminished by severe exercise, a finding consistent with recent evidence from rodent studies lipids may act as glial energy reserves extreme metabolic conditions. Using runners, Ramos-Cabrer, Cabrera-Zubizarreta et al. report detected significantly after fully recovered

Язык: Английский

---

Complex II ambiguities—FADH2 in the electron transfer system

Journal of Biological Chemistry, Год журнала: 2023, Номер 300(1), С. 105470 - 105470

Опубликована: Ноя. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Язык: Английский

---

Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation

Cell Death and Disease, Год журнала: 2024, Номер 15(5)

Опубликована: Май 21, 2024

Abstract Seipin is one key mediator of lipid metabolism that highly expressed in adipose tissues as well the brain. Lack gene, Bscl2 , leads to not only severe metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly lipids, facilitates nerve transmission important for coordination learning. Whether deficiency-leaded defects learning underlined by dysregulation its consequent myelin abnormalities remains be elucidated. In present study, we verified expression oligodendrocytes (OLs) their precursors, oligodendrocyte precursor cells (OPCs), demonstrated deficiency compromised OPC differentiation, which led decreased OL numbers, protein, myelinated fiber proportion thickness myelin. Deficiency resulted impaired spatial cognition mice. Mechanistically, suppressed sphingolipid metabolism-related genes OPCs caused morphological droplets (LDs), markedly impeded differentiation. Importantly, rosiglitazone, agonist PPAR-gamma, substantially restored phenotypes resulting from deficiency, such aberrant LDs, reduced sphingolipids, obstructed neurobehavioral defects. Collectively, study elucidated how deficiency-induced deficits via impairing myelination, may pave way developing novel intervention strategy treating metabolism-involved neurological disorders.

Язык: Английский

---

Inflammaging and Brain Aging

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10535 - 10535

Опубликована: Сен. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Язык: Английский

---

Functions and dysfunctions of oligodendrocytes in neurodegenerative diseases

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Дек. 20, 2022

Neurodegenerative diseases (NDDs) are characterized by the progressive loss of selectively vulnerable populations neurons, which is responsible for clinical symptoms. Although degeneration neurons a prominent feature that undoubtedly contributes to and defines NDD pathology, it now clear neuronal cell death no means mediated solely cell-autonomous mechanisms. Oligodendrocytes (OLs), myelinating cells central nervous system (CNS), enable rapid transmission electrical signals provide metabolic trophic support neurons. Recent evidence suggests OLs their progenitor population play role in onset progression NDDs. In this review, we discuss emerging suggesting OL lineage pathogenesis age-related We start with multiple atrophy, an well-known oligodendroglial then Alzheimer's disease (AD) Parkinson's (PD), NDDs have been thought as origins. Understanding functions dysfunctions might lead advent disease-modifying strategies against

Язык: Английский

---

Mitochondrial dysfunction in cognitive neurodevelopmental disorders: Cause or effect?

Mitochondrion, Год журнала: 2023, Номер 69, С. 18 - 32

Опубликована: Янв. 6, 2023

Язык: Английский

---

Oligodendrocytes in central nervous system diseases: the effect of cytokine regulation

Neural Regeneration Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 8, 2024

Abstract Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines involved nearly every aspect of cellular functions such as migration, survival, proliferation, differentiation. Oligodendrocytes the myelin-forming cells central nervous system play critical roles conduction action potentials, supply metabolic components for axons, other functions. Emerging evidence suggests that both oligodendrocytes oligodendrocyte precursor vulnerable to released under pathological conditions. This review mainly summarizes effects on lineage A comprehensive understanding contributes our diseases offers insights into treatment strategies.

Язык: Английский

---

The α- to γ-enolase switch: The role and regulation of γ-enolase during oligodendrocyte differentiation

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 140464 - 140464

Опубликована: Янв. 1, 2025

The glycolytic enzyme γ-enolase is a highly specific neuronal marker that known to replace ubiquitously expressed α-enolase in the brain. Moreover, has been shown exert neurotrophic activity, which regulated by cathepsin X, lysosomal peptidase. This study investigates role of and its regulation X during differentiation oligodendrocytes, are essential for normal brain function. We established protocol human oligodendroglioma (HOG) cell line demonstrated first time an α- switch occurs HOG differentiation. was confirmed expression markers underscoring oligodendrocyte overexpression enhanced differentiation, while silencing siRNA significantly decreased maturation marker. Further, regulatory cysteine peptidase on function found. Silencing changed morphology, altered markers, increased levels active form γ-enolase. Inhibiting similarly morphology These findings suggest modulates activity thereby influences thus

Язык: Английский

---

The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration

Acta Neuropathologica Communications, Год журнала: 2023, Номер 11(1)

Опубликована: Июнь 29, 2023

Neurodegenerative diseases encompass a heterogeneous group of conditions characterised by the progressive degeneration structure and function central or peripheral nervous systems. The pathogenic mechanisms underlying these are not fully understood. However, feature consists regional aggregation proteins in brain, such as accumulation β-amyloid plaques Alzheimer's disease (AD), inclusions hyperphosphorylated microtubule-binding tau AD other tauopathies, containing α-synuclein Parkinson's (PD), dementia with Lewy bodies (DLB) multiple system atrophy (MSA). Various thought to contribute disease, an increasing number studies implicate dysfunction oligodendrocytes (the myelin producing cells system) loss. Aberrant DNA methylation, most widely studied epigenetic modification, has been associated many neurodegenerative diseases, including AD, PD, DLB MSA, recent findings highlight aberrant methylation oligodendrocyte/myelin-related genes. Here we briefly review evidence showing that changes key neurodegeneration, explore relevance oligodendrocyte (dys)function. As is reversible, elucidating its involvement specific cell-types may bring opportunities for therapeutic interventions diseases.

Язык: Английский

---