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Abbreviations BBB: Bloodbrain barrier CNS: Central nervous system NVU: Neurovascular unit ECs: Endothelial cells CBF: Cerebrovascular blood flow TJs: Tight junctions AJs: Adherens junctions JAMs: Junctional adhesion molecules ZO: Zonula occludin VE-cadherin: Vascular endothelial cadherin PECAM-1: Platelet endothelial cell adhesion molecule-1 CMT: Carrier-mediated transport RMT: Receptor-mediated transport Mfsd2a: Major facilitator superfamily domain containing 2a Glut1: Glucose carrier 1 LRP1: Lipoprotein receptor 1 LRP2: Lipoprotein receptor 2 RAGE: Advanced glycation end products ABC transporters: ATP-binding cassette transporters P-gp: P-glycoprotein BCRP: Breast cancer resistance protein ICAMs: Intercellular adhesion molecules A: Amyloid-beta AQP4: Aquaporin-4 PDGF-BB: Platelet-derived growth factor-BB PDGFR: PDGF receptor- VEGF-A: Vascular endothelial growth factor-A VEGFR2: VEGF receptor 2 TGF-: Transforming growth factor- TGFR2: TGF- receptor 2 Ang1: Angiopoietin-1 Ang2: Angiopoietin-2 SMCs: Smooth muscle cells A2AR: Adenosine A2A receptors NA: Noradrenaline 2A: 2-Adrenergic receptors ACh: Acetylcholine MRs: Muscarinic ACh receptors NO: Nitric oxide mGluR: Metabotropic glutamate receptors AA: Arachidonic acid 20-HETE: 20-Hydroxy-eicosatetraenoic acid VGCCs: Voltage-gated calcium channels ET1: Endothelin 1 IGF1: Insulin-like growth factor 1 MRs: Muscarinic ACh receptors LPS: Lipopolysaccharide TNF-: Tumor necrosis factor-alpha IL-1: Interleukin-1 beta MAPK: Mitogen-activated protein kinase NF-B: Nuclear factor kappa-light-chain-enhancer of activated B cells IFN-: Interferon-gamma CCLs: Chemokine ligands MMPs: Matrix metalloproteinases ROCK: Rho-associated protein kinase VCAM-1: Vascular cell adhesion molecule 1 IgG: Immunoglobulin G GM-CSF: Granulocytemacrophage colony-stimulating factor C1q: Component subunit 1q A1: Reactive astrocytes Mac-1: Macrophage-1 antigen APOE4: Apolipoprotein E CypA: Cyclophilin A MCI: Mild cognitive impairment p-tau: Phosphorylated tau APOJ: Apolipoprotein J ISF: Interstitial fluid PCSK9: Proprotein convertase subtilisin/kexin type 9 BACE1: -Site amyloid precursor protein cleaving enzyme 1 NOXs: NADPH oxidases CAA: Cerebral amyloid angiopathy eNOS: Endothelial nitric oxide synthase LRP1-ICD: Intracellular domain of LRP1 Syn: Alpha-synuclein preformed fibrils PARP1: Poly (adenosine 5-diphosphate-ribose) polymerase 1 proBDNF: Pro-brain-derived neurotrophic factor 6-OHDA: 6-Hydroxydopamine COX-2: Cyclooxygenase-2 iNOS: Inducible nitric oxide synthase MCP-1: Chemoattractant protein-1 OLs: Oligodendrocytes EAE: Experimental autoimmune encephalomyelitis ROS: Reactive oxygen and nitrogen species NRs: NMDA receptors APC: Activated Protein C XQ-1H: 10-O-(N, N-dimethylaminoethyl) ginkgolide B methanesulfonate iPSCs: Induced pluripotent stem cells RvD: Resolvin D References Sweeney MD, Sagare AP, Zlokovic BV

These cardiac repair studies established TB-500 as one of the most extensively characterised peptide research tools for studying cardiac regeneration biology and provided the foundational evidence for thymosin beta-4s role as an endogenous cardiac repair mediator and establishing that actin-sequestering peptides have biological significance beyond cytoskeletal regulation in the context of cardiac injury response

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