Background: Neuroinflammation, and specifically microglia, plays an important but not-yet well-understood role in the pathophysiology of amyotrophic lateral sclerosis (ALS), constituting a potential therapeutic target for the disease. Recent studies have described the involvement of different microglial transcriptional patterns throughout neurodegenerative processes, identifying a new state of microglia: disease-associated microglia (DAM). The aim of this study is to investigate expression patterns of microglial-related genes in ALS spinal cord.
Methods: We analyzed mRNA expression levels via RT-qPCR of several microglia-related genes in their homeostatic and DAM state in postmortem tissue (anterior horn of the spinal cord) from 20 subjects with ALS-TDP43 and 19 controls donors from the Navarrabiomed Biobank.
Results: The expression levels of , , , and were found to be elevated in the spinal cord from ALS subjects versus controls (-value < 0.05). However, no statistically significant gene expression differences were observed for , and .
Conclusions: This study suggests that a DAM-mediated inflammatory response is present in ALS, and plays a significant role in immune function of microglia. It also supports the role of and in the physiopathology of ALS.
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http://dx.doi.org/10.3390/biomedicines11112994 | DOI Listing |
Nat Commun
January 2025
Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain.
Dysregulated microglia activation, leading to neuroinflammation, is crucial in neurodegenerative disease development and progression. We constructed an atlas of human brain immune cells by integrating nineteen single-nucleus RNA-seq and single-cell RNA-seq datasets from multiple neurodegenerative conditions, comprising 241 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) included 90,716 nuclei/cells and revealed nine populations distributed across all conditions.
View Article and Find Full Text PDFMicroglia modulate their cell state in response to various stimuli. Changes to cellular lipids often accompany shifts in microglial cell state, but the functional significance of these metabolic changes remains poorly understood. In human induced pluripotent stem cell-derived microglia, we observed that both extrinsic activation (by lipopolysaccharide treatment) and intrinsic triggers (the Alzheimer's disease-associated genotype) result in accumulation of triglyceride-rich lipid droplets.
View Article and Find Full Text PDFJ Neuroinflammation
January 2025
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Background: Traumatic brain injury (TBI) is characterized by high mortality and disability rates. Disease-associated microglia (DAM) are a newly discovered subtype of microglia. However, their presence and function in the acute phase of TBI remain unclear.
View Article and Find Full Text PDFPhytomedicine
January 2025
Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address:
Background: Ginkgo biloba leaf extract EGb 761® has shown clinical efficacy in patients with mild cognitive impairment and dementia. However, the pharmacological action of EGb 761® in Alzheimer's disease (AD) remains unclear and molecular mechanisms targeted in the brain are not completely understood.
Hypothesis/purpose: We aimed to investigate 1) the potential sex-dependent effects of oral administration of EGb 761® in 5xFAD mice, an AD mouse model, and 2) the underlying microglial subtype responsible for the observed anti-inflammatory effects in the brain.
Antioxidants (Basel)
December 2024
Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan.
Alzheimer's disease (AD) is a polygenic, multifactorial neurodegenerative disorder and remains the most prevalent form of dementia, globally. Despite decades of research efforts, there is still no effective cure for this debilitating condition. AD research has increasingly focused on transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) as a potential therapeutic target.
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