ArticleMolecular neurodegeneration2025
SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer's disease.
Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Controlling Epileptic Activity by Modulating Putrescine Metabolism.Biomolecules · 2026Article
- Single-cell-level perturbation-induced and condition-related signal estimation with batch effect removal using NDreamer.Briefings in bioinformatics · 2026Article
- Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology.Molecular psychiatry · 2026Review
- Metabolic-inflammatory memory: the common pathological basis and therapeutic targets of metabolic syndrome.Reviews in endocrine & metabolic disorders · 2026Review
- G Protein Inactivation as a Mechanism for Addiction Treatment.Biological psychiatry · 2026Article
- Astrocytic connexins in alcohol use disorder: mechanisms of neuroinflammation and therapeutic potential.Frontiers in psychiatry · 2026Review
- Comprehensive mapping of the signaling events evoked by SARS-CoV-2 variants delta and omicron in human astrocytes.Scientific reports · 2025Article
- Emerging roles of astrocytes in hippocampal circuitry and behavior.Frontiers in cellular neuroscience · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
backgroundAlzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and H
methodsUsing transcriptomics analysis, we identified two candidate enzymes, Aldehyde Dehydrogenase 1 family member A1 (ALDH1A1) and Sirtuin 2 (SIRT2) for the steps following MAOB in the astrocytic GABA production pathway. We used immunostaining, metabolite analysis and electrophysiology, both in vitro and in vivo, to confirm the participation of these enzymes in astrocytic GABA production. We checked for the presence of SIRT2 in human AD patients as well as the mouse model APP/PS1 and finally, we selectively ablated SIRT2 in the astrocytes of APP/PS1 mice to observe its effects on pathology.
resultsImmunostaining, metabolite analysis, and electrophysiology recapitulated the participation of ALDH1A1 and SIRT2 in GABA production. Inhibition of SIRT2 reduced the production of astrocytic GABA but not H
conclusionsOur study is the first to identify the specific role of SIRT2 in reactive astrogliosis and determine the specific pathway and metabolic step catalyzed by the enzyme. We determine the partial, yet significant role of ALDH1A1 in this process, thereby highlighting 2 new players the astrocytic GABA production pathway. Our findings therefore, offer SIRT2 as a new tool to segregate GABA from H
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