Beta-secretase 1 (BACE1)
Beta-secretase 1 (BACE1), also known as β-site amyloid precursor protein-cleaving enzyme 1, is a transmembrane aspartyl protease encoded by the BACE1 gene in humans.
Beta-secretase 1 (BACE1), also known as β-site amyloid precursor protein-cleaving enzyme 1, is a transmembrane aspartyl protease encoded by the BACE1 gene in humans. It is the rate-limiting enzyme responsible for the first proteolytic cleavage of amyloid precursor protein (APP), generating the soluble APP-beta fragment and the membrane-bound C99 stub that is subsequently cleaved by gamma-secretase to produce amyloid-beta (Aβ) peptides. The accumulation and aggregation of these Aβ peptides into plaques in the brain is a hallmark of Alzheimer's disease (AD) and forms the basis of the amyloid cascade hypothesis — currently the most widely accepted theoretical framework for understanding AD pathogenesis. Because BACE1 sits at a critical upstream node in this cascade, it has been intensively pursued as a therapeutic target for disease-modifying therapies in AD.
Beyond its role in amyloid processing, BACE1 is expressed broadly in the central nervous system and participates in the regulation of synaptic plasticity, myelination, and neuregulin signaling. Its inhibition, while therapeutically attractive, must therefore be carefully calibrated to avoid disrupting these physiological functions. This dual nature — as both a pathological driver and a functionally important enzyme — has made BACE1 one of the most challenging yet compelling targets in neuropharmacology, driving decades of medicinal chemistry, structural biology, and clinical investigation.
Where the papers sit
12 papers from the last 6 months study Beta-secretase 1 (BACE1) directly · updated from PubMed 11 Oct 2026
Study type 0 clinical trials · 6 human data · 6 preclinical
Themes 3 themes · 1 new direction
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Alzheimer’s Neuroprotection
Multi-target Alzheimer’s strategies pair AChE inhibition with amyloid-related mechanisms and neuroprotective effects. Donepezil-derived ligands and plant or fungal compounds are being evaluated as multifunctional candidates, often using inhibitory potency as an endpoint. Polydatin and related approaches emphasize oxidative stress and NF-κB/COX-2/IL-6 inflammatory signaling in hippocampal injury. Retinal proteomics extends the search for synaptic and cytoskeletal biomarkers that mirror brain pathology.
4 papers · 33.3%
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BACE1 Inhibitor Discovery
BACE1 inhibitor discovery is moving toward computationally guided prioritization, mechanistic modeling, and direct activity measurement. Molecular-dynamics studies focus on binding mechanisms and structural stability, while NeuroBACE-ML ranks potent candidates with explicit reliability assessment. A 19F MRI/NIR-FL nanoprobe adds noninvasive, turn-on imaging of BACE1 activity in Alzheimer’s disease. Together, these tools aim to reduce screening burden and connect inhibitor potency with target engagement in vivo.
3 papers · 25%
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Others — BACE1 Therapeutic Research
BACE1 appears across early therapeutic studies spanning Alzheimer’s drug discovery, cancer chemoradiation resistance, and natural-product screening. Meroterpenoids and other compounds are pursued as dual BACE1 and MAO-B or broader multitarget agents, while BACE1 overexpression is examined in rectal cancer treatment response. Computational personalization, Mendelian randomization, and data reuse occur alongside these pharmacology studies but do not form a shared biological direction. The cluster therefore offers scattered translational links rather than a unified research trajectory.
5 papers · 41.7%
BACE1 is presented as a rectal-cancer chemosensitizer through cleavage of ST6GAL1
The rectal-cancer chemoradiation model assumes that ST6GAL1-mediated sialylation of TNFR1 promotes treatment resistance; instead, the study identifies BACE1 overexpression as a way to abrogate that resistance, assigning BACE1 a role in remodeling tumor-cell sialylation and improving chemoradiation response rather than serving only as an Alzheimer disease amyloid-related target or inhibitor target 42373231Jun.
Papers
The 12 papers from the last 6 months that study Beta-secretase 1 (BACE1) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Alzheimer’s Neuroprotection (4)
- Therapeutic potential of Echinocactus grusonii and its associated endophytic fungus Aspergillus oryzae in neuroprotection: in vitro and in silico investigations. Scientific reports · 29 Jul 2026 PMID 42527432
- Retinal proteome changes mirror brain pathology and reveal synaptic and cytoskeletal dysfunction in Alzheimer's disease. Acta neuropathologica · 29 Jul 2026 PMID 42525245
- Polydatin inhibits hippocampal neurodegeneration in diabetic rats via modulation of oxidative stress and NF-kB/COX-2/IL-6 inflammatory pathway. Metabolic brain disease · 9 Jul 2026 PMID 42423809
- Donepezil-derived multi-target-directed ligands: design, synthesis, and anti-Alzheimer's evaluation. Bioorganic chemistry · 6 May 2026 PMID 42090829
BACE1 Inhibitor Discovery (3)
- Leveraging molecular dynamics to unravel the inhibition mechanism of potential β-secretase (BACE1) inhibitors. Physical chemistry chemical physics : PCCP · 5 Aug 2026 PMID 42555228
- A 19F MRI/NIR-FL Nanoprobe for "Turn-On" Imaging of β-Secretase (BACE1) Activity in Alzheimer's Disease. Angewandte Chemie (International ed. in English) · 8 Jun 2026 PMID 42259598
- NeuroBACE-ML: A reliability-aware screening framework for high-throughput prioritization of potent BACE1 inhibitors. Journal of molecular graphics & modelling · 20 Apr 2026 PMID 42008960
Others — BACE1 Therapeutic Research (5)
- Genetically predicted triglyceride levels and endometriosis risk: Mendelian randomization with exploratory multi-omics analyses. PloS one · 13 Aug 2026 PMID 42594068
- Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 Overexpression Abrogates ST6GAL1 Mediated Rectal Cancer Chemoradiation Resistance. Cancer genomics & proteomics · 29 Jun 2026 PMID 42373231
- Turning failure into success: how artificial intelligence can help personalize therapies and re-use patient data. Purinergic signalling · 29 May 2026 PMID 42213219
- Natural compounds from Fernandoa adenophylla (Wall. ex G.Don) Steenis as beta-secretase 1 and monoamine oxidase-b inhibitors: in vitro and computational evidence. Journal of computer-aided molecular design · 24 Apr 2026 PMID 42032388
- Discovery of Dual-Target Anti-Alzheimer's Filicinic Acid-Based Meroterpenoids from Hypericum japonicum Thunb. Journal of natural products · 17 Apr 2026 PMID 41996203
By study type
Human data, design not indexed (6)
- Genetically predicted triglyceride levels and endometriosis risk: Mendelian randomization with exploratory multi-omics analyses. PloS one · 13 Aug 2026 PMID 42594068
- Leveraging molecular dynamics to unravel the inhibition mechanism of potential β-secretase (BACE1) inhibitors. Physical chemistry chemical physics : PCCP · 5 Aug 2026 PMID 42555228
- Retinal proteome changes mirror brain pathology and reveal synaptic and cytoskeletal dysfunction in Alzheimer's disease. Acta neuropathologica · 29 Jul 2026 PMID 42525245
- Turning failure into success: how artificial intelligence can help personalize therapies and re-use patient data. Purinergic signalling · 29 May 2026 PMID 42213219
- Natural compounds from Fernandoa adenophylla (Wall. ex G.Don) Steenis as beta-secretase 1 and monoamine oxidase-b inhibitors: in vitro and computational evidence. Journal of computer-aided molecular design · 24 Apr 2026 PMID 42032388
- NeuroBACE-ML: A reliability-aware screening framework for high-throughput prioritization of potent BACE1 inhibitors. Journal of molecular graphics & modelling · 20 Apr 2026 PMID 42008960
Preclinical: animal, cell and lab studies (6)
- Therapeutic potential of Echinocactus grusonii and its associated endophytic fungus Aspergillus oryzae in neuroprotection: in vitro and in silico investigations. Scientific reports · 29 Jul 2026 PMID 42527432
- Polydatin inhibits hippocampal neurodegeneration in diabetic rats via modulation of oxidative stress and NF-kB/COX-2/IL-6 inflammatory pathway. Metabolic brain disease · 9 Jul 2026 PMID 42423809
- Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 Overexpression Abrogates ST6GAL1 Mediated Rectal Cancer Chemoradiation Resistance. Cancer genomics & proteomics · 29 Jun 2026 PMID 42373231
- A 19F MRI/NIR-FL Nanoprobe for "Turn-On" Imaging of β-Secretase (BACE1) Activity in Alzheimer's Disease. Angewandte Chemie (International ed. in English) · 8 Jun 2026 PMID 42259598
- Donepezil-derived multi-target-directed ligands: design, synthesis, and anti-Alzheimer's evaluation. Bioorganic chemistry · 6 May 2026 PMID 42090829
- Discovery of Dual-Target Anti-Alzheimer's Filicinic Acid-Based Meroterpenoids from Hypericum japonicum Thunb. Journal of natural products · 17 Apr 2026 PMID 41996203
Written from 12 PubMed abstracts, each one listed by PMID above. Published: 2026-07-02. Last written: 2026-08-26 by GPT. Drafted by language models from published abstracts; not medical advice.