ArticleMolecular neurodegeneration2022
Elevated ganglioside GM2 activator (GM2A) in human brain tissue reduces neurite integrity and spontaneous neuronal activity.
Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
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- Peripheral blood microarray-based transcriptomic and epigenetic analyses identify immune, inflammation, and metabolic dysregulation in Alzheimer's disease.NPJ dementia · 2026Article
- BoltzGen: Toward Universal Binder Design.bioRxiv : the preprint server for biology · 2025Article
- A PCD-related prognostic signature and the oncogenic role of TRIM8 in osteosarcoma progression.Journal of translational medicine · 2025Article
- Genetic and proteomic analysis identifies BAG3 as an amyloid-responsive regulator of neuronal proteostasis.Acta neuropathologica · 2025Article
- Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty.Research square · 2025Article
- Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Translating the Post-Mortem Brain Multi-Omics Molecular Taxonomy of Alzheimer's Dementia to Living Humans.bioRxiv : the preprint server for biology · 2025Article
- Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution.Cell reports · 2024Article
- Targeting GM2 Ganglioside Accumulation in Dementia: Current Therapeutic Approaches and Future Directions.Current molecular medicine · 2024Review
- Methods for the isolation and analysis of Aβ from postmortem brain.Frontiers in neuroscience · 2023Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's Disease (AD) affects millions globally, but therapy development is lagging. New experimental systems that monitor neuronal functions in conditions approximating the AD brain may be beneficial for identifying new therapeutic strategies.
methodsWe expose cultured neurons to aqueous-soluble human brain extract from 43 individuals across a spectrum of AD pathology. Multi-electrode arrays (MEAs) and live-cell imaging were used to assess neuronal firing and neurite integrity (NI), respectively, following treatments of rat cortical neurons (MEA) and human iPSC-derived neurons (iN) with human brain extracts.
resultsWe observe associations between spontaneous activity and Aβ42:40 levels, between neurite integrity and oligomeric Aβ, and between neurite integrity and tau levels present in the brain extracts. However, these associations with Aβ and tau do not fully account for the effects observed. Proteomic profiling of the brain extracts revealed additional candidates correlated with neuronal structure and activity. Neurotoxicity in MEA and NI assays was associated with proteins implicated in lysosomal storage disorders, while neuroprotection was associated with proteins of the WAVE regulatory complex controlling actin cytoskeleton dynamics. Elevated ganglioside GM2 activator (GM2A) associates with reductions in both NI and MEA activity, and cell-derived GM2A alone is sufficient to induce a loss of neurite integrity and a reduction in neuronal firing.
conclusionsThe techniques and data herein introduce a system for modeling neuronal vulnerability in response to factors in the human brain and provide insights into proteins potentially contributing to AD pathogenesis.
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