Beneficial Effect of Dimethyl Fumarate Drug Repositioning in a Mouse Model of TDP-43-Dependent Frontotemporal Dementia DOI Creative Commons
Ignacio Silva-Llanes, Raquel Martín-Baquero,

Alicia Berrojo-Armisen

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1072 - 1072

Published: Sept. 2, 2024

Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital limiting neurodegeneration, with its activation shown mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects a TAU-dependent FTD mouse model, reducing This suggests DMF repositioning potential for treatment. Until now, trial had been conducted analyze effect of on TDP-43-dependent FTD. In this study, we aimed determine efficacy TDP-43-related model that exhibits early cognitive impairment. Mice received oral every other day from presymptomatic symptomatic stages. By post-natal (PND) 60, improvement function already evident, becoming even more pronounced by PND90. enhancement correlates neuroprotection observed dentate gyrus reduction astrogliosis stratum lacunosum-moleculare zone. At prefrontal cortex (PFC) level, also observed, accompanied astrogliosis. Collectively, our results suggest application patients

Language: Английский

4,4′-Dimethoxychalcone Mitigates Neuroinflammation Following Traumatic Brain Injury Through Modulation of the TREM2/PI3K/AKT/NF-κB Signaling Pathway DOI Creative Commons
Mengran Wang, Rui Zhao,

Yue Su

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

Citations

0
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

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 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.

Language: Английский

Citations

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

et al.

Neurology International, Journal Year: 2025, Volume and Issue: 17(1), P. 6 - 6

Published: Jan. 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.

Language: Английский

Citations

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, Journal Year: 2025, Volume and Issue: unknown, P. 111287 - 111287

Published: Feb. 1, 2025

Language: Английский

Citations

0
Microglia in ALS: Insights into Mechanisms and Therapeutic Potential DOI Creative Commons

Silvano Bond,

Smita Saxena, Julieth A. Sierra-Delgado

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 421 - 421

Published: March 12, 2025

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to escalating muscle weakness, atrophy, and eventually paralysis. While neurons are most visibly affected, emerging data highlight microglia—the brain’s resident immune cells—as key contributors onset progression. Rather than existing in simple beneficial or harmful duality, microglia can adopt multiple functional states shaped internal external factors, including those ALS. Collectively, these disease-specific forms called disease-associated (DAM). Research using rodent models, patient-derived cells, human postmortem tissue shows that transition into DAM phenotypes, driving inflammation neuronal injury. However, cells also fulfill protective roles under certain conditions, revealing their adaptable nature. This review explores recent discoveries regarding multifaceted behavior ALS, highlights important findings link neuron deterioration, discusses therapies—some already used clinical trials—that aim recalibrate microglial functions potentially slow

Language: Английский

Citations

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

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167804 - 167804

Published: March 16, 2025

Language: Английский

Citations

0
Immune cell metabolic dysfunction in Parkinson’s disease DOI Creative Commons
Julian R Mark, Malú G. Tansey

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 24, 2025

Abstract Parkinson’s disease (PD) is a multi-system disorder characterized histopathologically by degeneration of dopaminergic neurons in the substantia nigra pars compacta . While etiology PD remains multifactorial and complex, growing evidence suggests that cellular metabolic dysfunction critical driver neuronal death. Defects metabolism related to energy production, oxidative stress, organelle health, protein homeostasis have been reported both immune cells PD. We propose these factors act synergistically drive aberrant inflammation CNS periphery PD, contributing hostile inflammatory environment which renders certain subsets vulnerable degeneration. This review highlights overlap between established deficits with emerging findings central peripheral cells. By discussing rapidly expanding literature on immunometabolic we aim draw attention potential biomarkers facilitate future development immunomodulatory strategies prevent or delay progression

Language: Английский

Citations

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

Katherine Neilsen

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

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

Yuhong Kou,

Ni Yang

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 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

Language: Английский

Citations

0
Spatial mapping of the AA-PGE2-EP axis in multiple sclerosis lesions DOI Creative Commons
Cathrin E. Hansen, Julia Konings, Gábor Tóth

et al.

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: April 29, 2025

Language: Английский

Citations

0