Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bax and Bcl-2 are prototypical members of a large family of Bcl-2-like proteins that play a key role in regulating programmed cell death in many cell types. The purpose of this review is to summarize recent findings about the role of Bcl-2 and Bax in regulating programmed cell death in the cerebellum during normal development and in a mouse model of cell autonomous and target-related cell death, the Lurcher mutant. Both Bcl-2 and Bax are expressed in the developing cerebellum and recent studies of Bcl-2 transgenic mice and Bcl-2 or Bax knock-out mutants have shown that both proteins are likely to play a role in regulating cell death among Purkinje cells, granule cells and olivary neurons. However, the evidence suggests that there are diverse cell death pathways in cerebellar neurons that vary depending on the cell type and cell death stimulus. For example, the number of Purkinje cells is increased by over 30% in one line of Bcl-2 overexpressing transgenics and in Bax knock-out mutants, suggesting that both proteins may be involved in naturally occurring Purkinje cell death. However, overexpression of Bcl-2 or deletion of Bax expression in heterozygous Lurcher mutants delays but does not prevent the cell autonomous death of Lurcher Purkinje cells. The deletion of Bax expression from granule cells does not affect their number in adult Bax knock-out mutants, suggesting that Bax is not involved in naturally occurring granule cell death. However, Bax does appear to be involved in granule cell target-related cell death since substantially more granule cells survive in Bax -/-: Lurcher double mutants than in control Lurcher mutants. In contrast, deletion of Bax expression in Lurcher mutants does not prevent olivary neuron target-related cell death in the Lurcher mutant while overexpression of Bcl-2 in olivary neurons rescues them from both target-related and naturally occurring cell death.
Cerebellum 2002 Dec
PMID:Cell death, Bcl-2, Bax, and the cerebellum. 1287 66

Cerebellar granule neurons (CGNs) constitute the most abundant neuronal population in the mammalian brain. Their postnatal generation and the feasibility to induce their apoptotic death in vitro make them an excellent model to study the effect of several neurotransmitters and neurotrophins. Here, we first review which factors are involved in the generation and proliferation of CGNs in the external granule layer (EGL) and in the regulation of their differentiation and migration to internal granule layer (IGL). Special attention was given to the role of several neurotrophins and the NMDA subtype of glutamate receptor. Then, using the paradigm of potassium deprivation in cultured CGNs, we address several extracellular factors that promote the survival of CGNs, with particular emphasis on the cellular mechanisms. The role of specific protein kinases leading to the regulation of transcription factors and recent data involving the small G protein family is also discussed. Finally, the participation of some members of Bcl-2 family and the inhibition of mitochondria-related apoptotic pathway is also considered. Altogether, these studies evidence that CGNs are a key model to understand the development and the survival of neuronal populations.
Cerebellum 2015 Jun
PMID:Delineating the factors and cellular mechanisms involved in the survival of cerebellar granule neurons. 2559 43

The purpose of this study is to determine the activation of the extrinsic and intrinsic apoptotic pathways in the cerebellum of rats exposed to amygdaloid electrical kindling. Western blot analyses were carried out for caspase-8 and caspase-9, Bid, Bax, and Bcl-2 in the cerebellum and immunohistochemistry of Bid, Bax, cytochrome C, and VDAC (voltage-dependent anion channels) in the cerebellar cortex of Wistar male rats with 0, 15, and 45 kindling stimulations. In the experimental group of 45 stimuli, we observed an increase in protein activation of caspase-9 and truncated Bid and Bax, in addition to a decrease in expression of pro-caspase-8 and the anti-apoptotic protein Bcl-2, determined by Western blot. Moreover, we observed a cytosolic immunopositivity for cytochrome C and a mitochondrial immunolocalization for truncated Bid and Bax in the group of 45 stimuli. In this work, we found an increase of caspase-8, a cysteine-protease that can activate caspase-3 triggering extrinsic apoptosis by signaling of death receptors. However, it also can activate the intrinsic pathway releasing Bid, which performs mitochondrial translocation of Bax, inactivating Bcl-2 and allowing the release of cytochrome C through the opening of the mitochondrial permeability transition pore, promoting the activation of caspase-9 which activates caspase-3, the main executor caspase of apoptosis. Therefore, it is concluded that there is an activation of the intrinsic and extrinsic apoptotic pathways in the cerebellum of rats exposed to the kindling model. Apoptosis signaling pathways can be analyzed as an important developing object of research about the epileptic activity. Graphical Abstract.
Cerebellum 2019 Aug
PMID:Activation of the Extrinsic and Intrinsic Apoptotic Pathways in Cerebellum of Kindled Rats. 3106 84