Oligodendrocyte progenitor cells in Alzheimer’s disease: from physiology to pathology DOI Creative Commons

Peibin Zou,

Chongyun Wu,

Timon Cheng‐Yi Liu

и другие.

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Ноя. 14, 2023

Abstract Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring contributing to the integrity of blood–brain barrier (BBB). However, under pathological circumstances Alzheimer’s disease (AD), brain’s microenvironment undergoes detrimental changes that significantly impact OPCs their functions. Starting OPC functions, we delve into transformation myelin-producing oligodendrocytes, intricate signaling interactions other central nervous system (CNS), fascinating process which influences function affects CNS homeostasis. Moreover, discuss essential role BBB highlight critical contribution forming CNS-protective barriers. In context AD, deterioration local brain is discussed, mainly focusing on neuroinflammation, oxidative stress, accumulation toxic proteins. The disturb delicate balance brain, impacting regenerative capacity compromising integrity. Under conditions, experience significant alterations migration proliferation, leading impaired differentiation a reduced ability produce mature oligodendrocytes. degeneration become increasingly active progressive neurodegeneration. Finally, summarize current therapeutic approaches targeting AD. Strategies revitalize senescence, modulate pathways enhance differentiation, explore potential avenues are promising alleviating AD function. conclusion, this review highlights indispensable involvement pathogenesis interplay between underscores complexity neurodegenerative diseases. Insights from studying conditions provide foundation for innovative strategies fostering Future research will advance our understanding management diseases, ultimately offering hope effective treatments improved quality life those affected by related disorders.

Язык: Английский

Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease DOI Creative Commons
Constanze Depp, Ting Sun, Andrew Octavian Sasmita

и другие.

Nature, Год журнала: 2023, Номер 618(7964), С. 349 - 357

Опубликована: Май 31, 2023

The incidence of Alzheimer's disease (AD), the leading cause dementia, increases rapidly with age, but why age constitutes main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and structural integrity myelin sheaths1, latter which associated secondary neuroinflammation2,3. As support axonal energy metabolism neuronal health4-7, we hypothesized that loss could be an upstream for amyloid-β (Aβ) deposition, central neuropathological hallmark AD. Here identify genetic pathways dysfunction demyelinating injuries as potent drivers amyloid deposition in mouse models Mechanistically, causes accumulation Aβ-producing machinery within swellings cleavage cortical precursor protein. Suprisingly, AD mice dysfunctional lack plaque-corralling microglia despite overall increase their numbers. Bulk single-cell transcriptomics defects show there a concomitant induction highly similar distinct disease-associated signatures specific to damage plaques, respectively. Despite successful induction, (DAM) usually clear plaques are apparently distracted nearby damage. Our data suggest working model whereby age-dependent promote Aβ plaque formation directly indirectly therefore factor. Improving oligodendrocyte health promising target delay development slow progression

Язык: Английский

Процитировано

236
Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17 DOI
Tal Iram, Fabian Kern, Achint Kaur

и другие.

Nature, Год журнала: 2022, Номер 605(7910), С. 509 - 515

Опубликована: Май 11, 2022

Язык: Английский

Процитировано

151
CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging DOI Creative Commons
Tuğberk Kaya, Nicola Mattugini, Lu Liu

и другие.

Nature Neuroscience, Год журнала: 2022, Номер 25(11), С. 1446 - 1457

Опубликована: Окт. 24, 2022

Abstract A hallmark of nervous system aging is a decline white matter volume and function, but the underlying mechanisms leading to pathology are unknown. In present study, we found age-related alterations oligodendrocyte cell state with reduction in total density murine matter. Using single-cell RNA-sequencing, identified interferon (IFN)-responsive oligodendrocytes, which localize proximity CD8 + T cells Absence functional lymphocytes decreased number IFN-responsive oligodendrocytes rescued loss, whereas T-cell checkpoint inhibition worsened response. addition, subpopulation lymphocyte-dependent, microglia vicinity summary, provide evidence that T-cell-induced, important modifiers aging.

Язык: Английский

Процитировано

143
Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration DOI

Yashi Mi,

Guoyuan Qi, Francesca Vitali

и другие.

Nature Metabolism, Год журнала: 2023, Номер 5(3), С. 445 - 465

Опубликована: Март 23, 2023

Язык: Английский

Процитировано

143
Insights into Alzheimer’s disease from single-cell genomic approaches DOI
Mitchell H. Murdock, Li‐Huei Tsai

Nature Neuroscience, Год журнала: 2023, Номер 26(2), С. 181 - 195

Опубликована: Янв. 2, 2023

Язык: Английский

Процитировано

104
TREM2 dependent and independent functions of microglia in Alzheimer’s disease DOI Creative Commons
Jinchao Hou, Yun Chen,

Gary E. Grajales‐Reyes

и другие.

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Дек. 23, 2022

Abstract Microglia are central players in brain innate immunity and have been the subject of extensive research Alzheimer’s disease (AD). In this review, we aim to summarize genetic functional discoveries that advanced our understanding microglia reactivity AD pathology. Given heightened risk posed by rare variants microglial triggering receptor expressed on myeloid cells 2 (TREM2), will focus studies addressing impact responses amyloid plaques, tauopathy demyelination pathologies mouse human. Finally, discuss implications recent TREM2 biology potential therapeutic strategies for AD.

Язык: Английский

Процитировано

96
Microglia regulation of central nervous system myelin health and regeneration DOI
Sarah Kent, Véronique E. Miron

Nature reviews. Immunology, Год журнала: 2023, Номер 24(1), С. 49 - 63

Опубликована: Июль 14, 2023

Язык: Английский

Процитировано

74
Fast-spiking parvalbumin-positive interneurons in brain physiology and Alzheimer’s disease DOI Creative Commons
Sara Hijazi, August B. Smit, Ronald E. van Kesteren

и другие.

Molecular Psychiatry, Год журнала: 2023, Номер 28(12), С. 4954 - 4967

Опубликована: Июль 7, 2023

Abstract Fast-spiking parvalbumin (PV) interneurons are inhibitory with unique morphological and functional properties that allow them to precisely control local circuitry, brain networks memory processing. Since the discovery in 1987 PV is expressed a subset of fast-spiking GABAergic neurons, our knowledge complex molecular physiological these cells has been expanding. In this review, we highlight specific neurons fire at high frequency reliability, enabling network oscillations shape encoding, consolidation retrieval memories. We next discuss multiple studies reporting neuron impairment as critical step neuronal dysfunction cognitive decline mouse models Alzheimer’s disease (AD). Finally, propose potential mechanisms underlying AD argue early changes activity could be causal AD-associated significant contributor pathogenesis.

Язык: Английский

Процитировано

52
Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice DOI Creative Commons
Andrew Octavian Sasmita, Constanze Depp,

T. I. Nazarenko

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(9), С. 1668 - 1674

Опубликована: Авг. 5, 2024

Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant oligodendrocytes (OLs). By cell-type-specific deletion Bace1 a humanized knock-in AD model, APP

Язык: Английский

Процитировано

31
VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors DOI Creative Commons

Soo Ji Baek,

Jin‐Sung Park, Jinhyun Kim

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Фев. 14, 2022

Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of cerebellum to symptoms remains be elucidated. Here, we demonstrated crucial role neurons projecting ventral tegmental area (VTA) development chronic stress-induced behavioral mice. Chronic chemogenetic activation inhibitory Purkinje cells crus I suppressed c-Fos expression DN and an increase immobility tail suspension test or forced swimming test, which were triggered by application. The combination adeno-associated virus-based circuit mapping electrophysiological recording identified network connections from VTA via dentate nucleus (DN) deep nuclei. Furthermore, inhibition specific that project prevented stressed mice showing such depression-like behavior, whereas these alone changes comparable with behaviors Our results indicate VTA-projecting proactively regulate raising possibility may effective target for prevention depressive disorders human.

Язык: Английский

Процитировано

70