Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tambaleante (tbl/tbl) is a mutant mouse that carries a spontaneous Gly483Glu substitution in the HERC1 (HECT domain and RCC1 domain) E3 ubiquitin ligase protein (HERC1). The tbl/tbl mutant suffers an ataxic syndrome given the almost complete loss of cerebellar Purkinje cells during adult life. More recent analyses have identified alterations at neuromuscular junctions in these mice, as well as in other neurons of the central nervous system, such as motor neurons in the spinal cord, or pyramidal neurons in the hippocampal CA3 region and the neocortex. Accordingly, the effect of the tbl/tbl mutation apparently extends to other regions of the nervous system far from the cerebellum. As HERC1 mutations in humans have been correlated with intellectual impairment, we studied the effect of the tbl/tbl mutation on learning. Using a behavioral test, ex vivo electrophysiological recordings, immunohistochemistry, and Golgi method, we analyzed the associative learning in the lateral amygdala of the tbl/tbl mouse. The tbl/tbl mice perform worse than wild-type animals in the passive avoidance test, and histologically, the tbl/tbl mice have more immature forms of dendritic spines. In addition, LTP cannot be detected in these animals and their STP is dampened, as is their glutamatergic input to the lateral amygdala. Together, these data suggest that HERC1 is probably involved in regulating synaptic function in the amygdala. Indeed, these results indicate that the tbl/tbl mutation is a good model to analyze the effect of alterations to the ubiquitin-proteasome pathway on the synaptic mechanisms involved in learning and its defects.
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PMID:Mutation of the HERC 1 Ubiquitin Ligase Impairs Associative Learning in the Lateral Amygdala. 2810 68

Storage of long-term memory requires not only protein synthesis but also protein degradation. In this article, we overview recent publications related to this issue, stressing that the balanced actions of protein synthesis and degradation are critical for long-term memory formation. We particularly focused on the brain-derived neurotrophic factor signaling that leads to protein synthesis; proteasome- and autophagy-dependent protein degradation that removes molecular constraints; the role of Fragile X mental retardation protein in translational suppression; and epigenetic modifications that control gene expression at the genomic level. Numerous studies suggest that an imbalance between protein synthesis and degradation leads to intellectual impairment and cognitive disorders.
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PMID:Balanced actions of protein synthesis and degradation in memory formation. 3141 3