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Abbreviations AD: Alzheimers disease AHN: Adult hippocampal neurogenesis aNSCs: Activated neural stem cells APP: Amyloid precursor protein A: Amyloid BDNF: Brain-derived neurotrophic factor bHLH: Basic helix-loop-helix BMP: Bone morphogenetic protein BLBP: Brain lipid-binding protein CCK: Cholecystokinin CDK: Cyclin-dependent kinase DCX: Doublecortin X DG: Dentate gyrus Ebd1: Earthbound1/jerky EE: Environmental enrichment GABA: -Aminobutyric acid Gadd45: Growth arrest and DNA damage 45 gamma GC: Granule cells GCL: Granule cell layer GFAP: Glial fibrillary acidic protein IGF-1: Insulin-like growth factor 1 Klf9: Kruppel-like factor 9 MC: Mossy cells MCT1: Monocarboxylic acid transporter 1 MFGE8: Milk fat globule-epidermal growth factor (EGF) 8 mGluR5: Metabotropic glutamate receptor subtype 5 MOL: Molecular layer NGF: Nerve growth factor Ngn2: Neurogenin2 NMDA: N -Methyl-d-aspartate NPC: Neural progenitor cells NSCs: Neural stem cells NT-3: Neurotrophin-3 PV: Parvalbumin qNSCs: Quiescent neural stem cells REST: RE-1 silencing transcription factor SGZ: Subgranular zone SOX2: Sry-related HMG box transcription factor 2 SST: Somatostatin TLR4: Toll-like receptor 4 VEGF: Vascular endothelial growth factor References Zheng JY et al (2017) Chronic Estradiol administration during the early stage of Alzheimers disease pathology rescues adult hippocampal neurogenesis and ameliorates cognitive deficits in Abeta1-42 mice

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This method is based on spontaneous isopeptide bonding between two protein parts derived from Gram-positive bacteria, achieving high conjugation efficiencies (up to 90%) but requiring fusion of large moieties ( e.g ., ~ 12 kDa Catcher), which can introduce challenges similar to genetic fusion