TY - JOUR
T1 - Membrane-permeable Bcl-xL prevents MPTP-induced dopaminergic neuronal loss in the substantia nigra
AU - Dietz, Gunnar P.H.
AU - Stockhausen, Kerstin V.
AU - Dietz, Birgit
AU - Falkenburger, Björn H.
AU - Valbuena, Paola
AU - Opazo, Felipe
AU - Lingor, Paul
AU - Meuer, Katrin
AU - Weishaupt, Jochen H.
AU - Schulz, Jörg B.
AU - Bähr, Mathias
PY - 2008/2
Y1 - 2008/2
N2 - The anti-apoptotic Bcl-xL is a promising agent to prevent neurodegeneration in Parkinson's disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl-xL to a peptide that allows its delivery across biological membranes and the blood-brain barrier. We tested the fusion protein in two models of Parkinson's Disease. Cell-permeable Bcl-x L protected neuroblastoma cells from the selective neurotoxin 1-methyl-4-phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta. Hence, we present that a cell-permeable form of an anti-apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases.
AB - The anti-apoptotic Bcl-xL is a promising agent to prevent neurodegeneration in Parkinson's disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl-xL to a peptide that allows its delivery across biological membranes and the blood-brain barrier. We tested the fusion protein in two models of Parkinson's Disease. Cell-permeable Bcl-x L protected neuroblastoma cells from the selective neurotoxin 1-methyl-4-phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta. Hence, we present that a cell-permeable form of an anti-apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases.
KW - Apoptosis
KW - Cell penetrating peptide
KW - HIV-Tat
KW - Primary dopaminergic midbrain culture
KW - Protein transduction domain
KW - Trojan horse peptide
UR - http://www.scopus.com/inward/record.url?scp=38049146545&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2007.05028.x
DO - 10.1111/j.1471-4159.2007.05028.x
M3 - Article
C2 - 17995935
AN - SCOPUS:38049146545
SN - 0022-3042
VL - 104
SP - 757
EP - 765
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -