bcl-2 transgene expression can protect neurons against developmental and induced cell death.

Farlie, Peter G.; Dringen, Ralf; Rees, Sandra; Kannourakis, George; Bernard, Ora

doi:10.1073/pnas.92.10.4397

Cited by 240 publications

(153 citation statements)

References 42 publications

(41 reference statements)

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“…We have shown previously that overexpression of bcl-2 in Grid2 Lc/ϩ olivary neurons will rescue most of the olivary neurons from target-related cell death (Zanjani et al, 1998b). This result is consistent with previous studies showing in vitro rescue of neurons from trophic factor withdrawal (Garcia et al, 1992;Allsopp et al, 1993;Batistatou et al, 1993) and in vivo rescue of neurons from axotomy or ischemia by bcl-2 overexpression Martinou et al, 1994;Farlie et al, 1995;Bonfanti et al, 1996;De Bilbao and Dubois-Dauphin, 1996) or deletion of Bax expression (Deckwerth et al, 1996;White et al, 1998).…”

Section: Granule Cell Survival and Olivary Neuron Deathsupporting

confidence: 82%

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

2000

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Lurcher is a gain-of-function mutation in the ␦2 glutamate receptor gene (Grid2) that turns the receptor into a leaky ion channel. The expression of the Lurcher gene in heterozygous (Grid2 Lc/ϩ ) mutants induces the death of almost all Purkinje cells starting from the second postnatal week. Ninety percent of the granule cells and 60-75% of the inferior olivary neurons die because of the loss of their target neurons, the Purkinje cells. The apoptotic nature of the neurodegeneration has been demonstrated previously by the presence of activated caspase-3 and DNA fragmentation. Bax, a pro-apoptotic gene of the Bcl-2 family, has been shown to be involved in developmental neuronal death. To study the role of Bax in Grid2 Lc/ϩ neurodegeneration, double mutants with Grid2 Lc/ϩ mice and Bax knock-out mice (BaxϪ/Ϫ) were generated. Bax deletion had no effect on the death of Purkinje cells and inferior olivary neurons, although a temporary rescue of some Purkinje cells could be detected in P15 Grid2 Lc/ϩ ;BaxϪ/Ϫ animals. From postnatal day 15 (P15) to P60, the number of granule cells in Grid2 Lc/ϩ ;BaxϪ/Ϫmice did not significantly change and was significantly increased compared with the number found in Grid2 Lc/ϩ ;Baxϩ/ϩ mice. Granule cell number in P60 Grid2 Lc/ϩ ;BaxϪ/Ϫ mice corresponded to 70% of the number found in wild-type mice. Our results show that Bax inactivation in Grid2 Lc/ϩ mice does not rescue intrinsic Purkinje cell death or the target-related cell death of olivary neurons, but Bax inactivation does inhibit persistently target-related cell death in cerebellar granule cells.

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Section: Granule Cell Survival and Olivary Neuron Deathsupporting

confidence: 82%

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

2000

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“…Bcl-2 expression, which directly exerts anti-apoptotic effects through Akt/PI3k pathways (Farlie et al, 1995), appears primarily affected by SCF-c-kit binding (McGill et al, 2002). Thus, Bcl-2 protein level was quantitatively measured to explore whether anti-apoptotic effects of SCF in 6-OHDA-exposed dopaminergic neurons was mediated by Bcl-2 upregulation (supplemental Fig.…”

Section: In Vitro Studymentioning

confidence: 99%

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

Yasuhara¹,

Matsukawa²,

Hara³

et al. 2006

J. Neurosci.

260

200

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“…One of the features of Bcl-2 family is the formation of homo-and heterodimers whose relative abundance coincides with either cell death or survival. 3 Bcl-2 has been shown to rescue various neuronal populations from cell death due to neurotrophic factor deprivation, 4 axotomy 5 or other insults. 6 Consistent with its apparent role in controlling developmental cell death, Bcl-2 is expressed at high levels in the developing central nervous system and eye.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous system

Krajewska

Zapata

et al. 2002

Cell Death Differ

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We have used immunohistochemistry and immunoblotting to examine the expression of Bid and four other Bcl-2 family proteins (Bcl-2, Bcl-X, Bax and Bak)in the developing and adult murine central nervous system (CNS). Bid protein is widespread in embryonic and postnatal brain, and its expression is maintained at a high level late into the adulthood. Bid is expressedbothinthegermdisc,earlyneuraltube,proliferating stem cells of ventricular zones, and in postmitotic, differentiated neurons of the developing central and peripheral nervous system. As the differentiation proceeds, the neurons express higher levels of Bid than the stem cells of the paraventricular zone. Both in embryonic and postnatal life, Bid protein is present in the most vital regions of brain, such as the limbic system, basal ganglia, mesencephalic tectum, Purkinje cells in cerebellum, and the ventral columns of spinal cord. The p15 cleaved form of Bid was detectable in the brain specimens at fetal stages of development, consistent with caspasemediated activation of this pro-apoptotic Bcl-2 family protein.Among the Bcl-2 family proteins only Bid and Bcl-X L continue to be expressed at high levels in the adult brain.

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bcl-2 transgene expression can protect neurons against developmental and induced cell death.

Cited by 240 publications

References 42 publications

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

Transplantation of Human Neural Stem Cells Exerts Neuroprotection in a Rat Model of Parkinson's Disease

Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous system

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