2001
DOI: 10.1074/jbc.m108930200
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Inhibition of Axotomy-induced Neuronal Apoptosis by Extracellular Delivery of a Bcl-XL Fusion Protein

Abstract: Bcl-2 and Bcl-XL prevent neuronal apoptosis during development, neurodegenerative disease, and trauma. To test a new anti-apoptosis strategy for neuroprotection, we engineered nontoxic components of anthrax toxin into a Bcl-XL delivery system. Delivery of Bcl-XL by this system prevented apoptosis of cultured rat cerebellar granule cells and macrophages, and the prevention depended on both the Bcl-XL and the anthrax toxin receptor binding/translocation moieties. Furthermore, neuronal death in vivo in a retinal … Show more

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Cited by 45 publications
(43 citation statements)
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References 69 publications
(79 reference statements)
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“…Penetratin [17], polylysine [18,19], polyarginine [20], Tat PTD [16,21], HSV VP22 [22][23][24], Kaposi FGF [25], Syn B1 [26], FGF-4 [27,28], nuclear localization signal (NLS) [29], and anthrax toxin derivative 254-amino acids (aa) peptide segment [30], diphtheria toxin 'R ' binding domain [31], MPG (HIV gp41/SV40 Tag NLS) [32], pep-1 [33], WR peptide [34], and exotoxin A [35] have all been used successfully in protein transductions. The first cargo transduction was achieved by using a homeodomain of Antennapedia (Antp) [36], which transduced neurons and other cells.…”
Section: Cell Penetrating Peptides (Cpps) For Protein Deliverymentioning
confidence: 99%
“…Penetratin [17], polylysine [18,19], polyarginine [20], Tat PTD [16,21], HSV VP22 [22][23][24], Kaposi FGF [25], Syn B1 [26], FGF-4 [27,28], nuclear localization signal (NLS) [29], and anthrax toxin derivative 254-amino acids (aa) peptide segment [30], diphtheria toxin 'R ' binding domain [31], MPG (HIV gp41/SV40 Tag NLS) [32], pep-1 [33], WR peptide [34], and exotoxin A [35] have all been used successfully in protein transductions. The first cargo transduction was achieved by using a homeodomain of Antennapedia (Antp) [36], which transduced neurons and other cells.…”
Section: Cell Penetrating Peptides (Cpps) For Protein Deliverymentioning
confidence: 99%
“…The first in vivo evidence that the chimera inhibited apoptosis came from animal studies in rat optic nerves [6]. Following injury and transection, the number of pyknotic cells decrease significantly in tissues treated with Lfn-BCL-X L .…”
Section: Ced For Stroke: Engineering Chimeric Proteins To Safeguard Nmentioning
confidence: 99%
“…The efficient endosomal escape of lethal factor and edema factor has been used for the delivery of fusion proteins containing the protective antigen-binding moiety of lethal factor to deliver other enzymes to the cytosol. These fusion proteins have been successfully utilized for various tumor-therapy approaches [30,42,43], the delivery of reporter proteins [44] and the delivery of anti-apoptotic Bcl-x L [45].…”
Section: Endosomal Escapementioning
confidence: 99%