ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Depletion of GGA1 and GGA3 mediates postinjury elevation of BACE1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Traumatic Brain Injury and the Road to Alzheimer's Disease.Biomedicines · 2026Review
- GGAs: Regulation of Multiple Sorting Pathways and Potential Association With Human Diseases.Journal of cellular and molecular medicine · 2026Review
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- Review
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- E2F1 Mediates Traumatic Brain Injury and Regulates BDNF-AS to Promote the Progression of Alzheimer's Disease.Neurotoxicity research · 2024Article
- Article
- Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- The Emergence of Model Systems to Investigate the Link Between Traumatic Brain Injury and Alzheimer's Disease.Frontiers in aging neuroscience · 2021Review
- Article
- Regulation of BACE1 expression after injury is linked to the p75 neurotrophin receptor.Molecular and cellular neurosciences · 2019Article
- BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- BACE1 elevation engendered by GGA3 deletion increases β-amyloid pathology in association with APP elevation and decreased CHL1 processing in 5XFAD mice.Molecular neurodegeneration · 2018Article
- Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1.Neurobiology of aging · 2017Article
- Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Physiological Functions of the β-Site Amyloid Precursor Protein Cleaving Enzyme 1 and 2.Frontiers in molecular neuroscience · 2017Review
- The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation.The Journal of biological chemistry · 2016Article
- Neuronal human BACE1 knockin induces systemic diabetes in mice.Diabetologia · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) is one of the most robust environmental risk factors for Alzheimer's disease (AD). Compelling evidence is accumulating that a single event of TBI is associated with increased levels of Aβ. However, the underlying molecular mechanisms remain unknown. We report here that the BACE1 interacting protein, GGA3, is depleted while BACE1 levels increase in the acute phase after injury (48 h) in a mouse model of TBI. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3-null mice. We next found that head trauma potentiates BACE1 elevation in GGA3-null mice in the acute phase after TBI, and discovered that GGA1, a GGA3 homolog, is a novel caspase-3 substrate depleted at 48 h after TBI. Moreover, GGA1 silencing potentiates BACE1 elevation induced by GGA3 deletion in neurons in vitro, indicating that GGA1 and GGA3 synergistically regulate BACE1. Accordingly, we found that levels of both GGA1 and GGA3 are depleted while BACE1 levels are increased in a series of postmortem AD brains. Finally, we show that GGA3 haploinsufficiency results in sustained elevation of BACE1 and Aβ levels while GGA1 levels are restored in the subacute phase (7 d) after injury. In conclusion, our data indicate that depletion of GGA1 and GGA3 engender a rapid and robust elevation of BACE1 in the acute phase after injury. However, the efficient disposal of the acutely accumulated BACE1 solely depends on GGA3 levels in the subacute phase of injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.