TREM2 deficiency exacerbates cognitive impairment by aggravating α-Synuclein-induced lysosomal dysfunction in Parkinson’s disease DOI Creative Commons

Baoyu Zhu,

Jiezhu Feng,

Xiaomei Liang

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Май 20, 2025

Abstract Cognitive impairment in Parkinson’s disease (PD) is a widespread and rapidly progressive feature that impacts prognosis. Although TREM2 has been implicated neuroprotection across various neurodegenerative diseases, its specific role PD remains to be clarified. In this study, we first detected the hippocampus of human specimens mutant A53T α-Synuclein transgenic mice (A53T mice), found significant increase number + microglia. To evaluate effects deficiency, TREM2-deficient (TREM2 -/- /A53T mice) were generated. these mice, exacerbated cognitive impairment, neurodegeneration, disruption synaptic plasticity, accumulation pathological (α-Syn) observed, without any motor dysfunction. Despite increased infiltration activated microglia surrounding α-Syn aggregates, lysosomal dysfunction was aggravated mice. addition, transcriptional analyses vitro experiments further knockdown inhibited nuclear distribution TFEB via ERK1/2 pathway, exacerbating α-Syn-induced causing more accumulation. Finally, HT22 cells cocultured with BV-2 pretreated recombinant preformed fibrils (PFFs). The coculture showed PFFs enhanced phosphorylation promoted apoptosis inhibiting degradation. conclusion, deficiency exacerbates by microglial dysfunction, identifying as potential therapeutic target.

Язык: Английский

CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis DOI Open Access
Luca Muzio, Jessica Perego

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4865 - 4865

Опубликована: Апрель 29, 2024

Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both parenchyma and non-parenchymal tissue (meninges, perivascular space, choroid plexus) are richly populated in resident immune cells. The advent of more powerful tools multiplex immunophenotyping, such as single-cell RNA sequencing technique upscale multiparametric flow mass spectrometry, helped discriminating between infiltrating cells and, above all, different spectrum phenotypes distinguishing border-associated macrophages. Here, we focus our attention on innate players their primary role homeostasis pathological neuroinflammation neurodegeneration, two key interconnected aspects immunopathology multiple sclerosis.

Язык: Английский

Процитировано

3
Microglial lipid phosphatase SHIP1 limits complement-mediated synaptic pruning in the healthy developing hippocampus DOI Creative Commons

A. Matera,

Anne‐Claire Compagnion, Chiara Pedicone

и другие.

Immunity, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

3
Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines DOI Creative Commons

Negin Imani Farahani,

Lisa Lin,

Shama Nazir

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Янв. 6, 2025

Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures optimize the effectiveness of disease prevention and treatment. This approach is favorable in context brain disorders, which are often heterogeneous their pathophysiological features, patterns progression treatment response, resulting limited therapeutic standard-of-care. Here we highlight transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models poised play advancing precision for particularly emerging innovations improve relevance hiPSC physiology. hiPSCs derived from accessible patient somatic cells can produce various types tissues; current efforts increase complexity these models, incorporating region-specific tissues non-neural microenvironment, providing increasingly relevant insights into human-specific neurobiology. Continued advances tissue engineering combined with genomics, high-throughput screening imaging strengthen physiological thus ability uncover mechanisms, vulnerabilities, fluid-based biomarkers will have real impact neurological True understanding, however, necessitates integration hiPSC-neural biophysical data, including quantitative neuroimaging representations. We discuss recent cellular neuroscience provide direct connections through generative AI modeling. Our focus great potential synergy between pave way personalized becoming a viable option suffering neuropathologies, rare epileptic neurodegenerative disorders.

Язык: Английский

Процитировано

0
The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation DOI Creative Commons
Srishti Kala, Andrew G. Strutz, Moriah E. Katt

и другие.

Neurology International, Год журнала: 2025, Номер 17(1), С. 6 - 6

Опубликована: Янв. 13, 2025

Neuroinflammation is a blanket term that describes the body’s complex inflammatory response in central nervous system (CNS). It encompasses phenotype shift to proinflammatory state, release of cytokines, recruitment peripheral immune cells, and wide variety other processes. has been implicated nearly every major CNS disease ranging from Alzheimer’s brain cancer. Understanding modeling neuroinflammation critical for identification novel therapeutic targets treatment diseases. Unfortunately, translation findings non-human models left much be desired. This review systematically discusses role human pluripotent stem cell (hPSC)-derived glia supporting cells within CNS, including astrocytes, microglia, oligodendrocyte precursor pericytes, endothelial describe state field hope future discoveries. hPSC-derived offer an expanded potential study pathobiology immunomodulatory cascades impact progression. While progress made development models, there explore application these understand CNS.

Язык: Английский

Процитировано

0
Microglia-derived sEV: Friend or foe in the pathogenesis of cognitive impairment DOI
Lilin Chen, Wei Wang

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2025, Номер unknown, С. 111287 - 111287

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy DOI
Sheyla Velasco, Idoia Gallego, Lorena Olivares‐González

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 185, С. 117962 - 117962

Опубликована: Март 11, 2025

Язык: Английский

Процитировано

0
Electrical stimulation promotes peripheral nerve regeneration by upregulating glycolysis and oxidative phosphorylation DOI
Nannan Zhang, Xiaoying Yao, Qingqing Zhang

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(5), С. 167804 - 167804

Опубликована: Март 16, 2025

Язык: Английский

Процитировано

0
Metabolic control of microglia in health and disease DOI
Gloria Colombo, Katia Monsorno, Rosa Chiara Paolicelli

и другие.

Handbook of clinical neurology, Год журнала: 2025, Номер unknown, С. 143 - 159

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Choroidal Neovascularization Is Suppressed With Activation of TREM2 in Mononuclear Phagocytes DOI Creative Commons
Hitomi Yagi, Myriam Boeck,

Katherine Neilsen

и другие.

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

BACKGROUND: Mononuclear phagocytes contribute to pathological angiogenesis in age-related macular degeneration, a leading worldwide cause of visual impairment. However, the mechanisms that orchestrate functions mononuclear remain poorly understood. TREM2 (triggering receptor on myeloid cells 2) has been shown be crucial for activation atherosclerosis, fatty liver disease, and Alzheimer disease. The objective this study was investigate role degeneration. METHODS: C57BL/6J Trem2 knockout mice were subjected laser-induced choroidal neovascularization, model neovascular Purified bovine sulfatide agonist anti-TREM2 antibody used activate signaling. expression or downstream signals assessed with immunohistochemistry qPCR. In vitro murine macrophage RAW264.7 direct impact inflammatory phagocytic responses. RESULTS: We found pharmacological suppressed neovessel formation. TNF (tumor necrosis factor) subsequently promoted phagocytosis. CONCLUSIONS: These findings demonstrate suppresses proinflammatory response, promotes phagocytosis, impedes Our provides insight into critical angiogenesis.

Язык: Английский

Процитировано

0
Microglia efferocytosis: an emerging mechanism for the resolution of neuroinflammation in Alzheimer’s disease DOI Creative Commons
Yongping Chen,

Yuhong Kou,

Ni Yang

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Март 30, 2025

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by significant neuroinflammatory responses. Microglia, the immune cells of central nervous system, play crucial role in pathophysiology AD. Recent studies have indicated that microglial efferocytosis an important mechanism for clearing apoptotic and cellular debris, facilitating resolution neuroinflammation. This review summarizes biological characteristics microglia mechanisms underlying efferocytosis, including factors signaling pathways regulate interactions between other influence this process, neuroinflammation Furthermore, we explore AD from three perspectives: its impact on clearance amyloid plaques, regulation neuroinflammation, effects neuroprotection. Finally, summarize current research status enhancing to alleviate improve AD, as well future challenges approach therapeutic strategy

Язык: Английский

Процитировано

0