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

Abstract

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

Learning interpretable cellular embedding for inferring biological mechanisms underlying single-cell transcriptomics

“…In Alzheimer's, amyloid plaques and tau tangles disrupt this, leading to cognitive decline. OPCs play a role in signal transmission by interacting with neurons and forming neuronal-OPC synapses, which exhibit synaptic plasticity similar to that observed in neuron-neuron synapses 34 . However, while iGTP identifies signals in OPCs, ssGSEA fails to detect much activity (see Fig.…”

The Genomic Intersection of Oligodendrocyte Dynamics in Schizophrenia and Aging Unravels Novel Pathological Mechanisms and Therapeutic Potentials

“…These processes are sensitive to a myriad of internal and external stimuli, thereby facilitating adaptive responses to neuronal activity and compensating for myelin loss due to injury or disease [13][14][15]. OLs originate from OPCs through a regulated differentiation pathway, ensuring a balance between the production of new OLs and the preservation of the OPC pool for future needs [16][17][18]. However, for reasons unknown across the different myelin pathologies, the capacity for OPC differentiation drastically declines during aging as we and others have described [19][20][21].…”