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Article
Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition
Although circadian and sleep disorders are frequently associated with autism spectrum disorders (ASD), it remains elusive whether clock gene disruption can lead to autistic-like phenotypes in animals. The esse...
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Article
Open AccessCholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway
This is a summary of the virtual presentation given at the 2021 meeting of the Society for Research on the Cerebellum and Ataxias, https://www.meetings.be/SRCA2021/
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Article
Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications
Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive mot...
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Article
Open AccessThe ataxin-1 interactome reveals direct connection with multiple disrupted nuclear transport pathways
The expanded polyglutamine (polyQ) tract form of ataxin-1 drives disease progression in spinocerebellar ataxia type 1 (SCA1). Although known to form distinctive intranuclear bodies, the cellular pathways and p...
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Article
Open AccessTargeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism
Autism spectrum disorder (ASD) encompasses wide-ranging neuropsychiatric symptoms with unclear etiology. Although the cerebellum is a key region implicated in ASD, it remains elusive how the cerebellar circuit...
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Chapter
Spinocerebellar Ataxia Type 1: Molecular Mechanisms of Neurodegeneration and Preclinical Studies
Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, inherited disease that leads to degeneration of Purkinje cells of the cerebellum and culminates in death 10–30 years after disease onset. SCA1 is caused ...
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Article
Polyglutamine spinocerebellar ataxias — from genes to potential treatments
Among the diverse group of dominantly inherited spinocerebellar ataxias (SCAs), those attributable to the expansion of polyglutamine (polyQ)-encoding CAG repea...
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Article
Disruption of the ATXN1–CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans
Huda Zoghbi and colleagues report that loss of the ATXN1–CIC protein complex in the develo** mouse forebrain results in hyperactivity and defects in learning and memory. Loss of Cic in specific brain regions ca...
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Article
Tolerance is established in polyclonal CD4+ T cells by distinct mechanisms, according to self-peptide expression patterns
CD4+ T cell tolerance can be enforced by various mechanisms. Jenkins and colleagues use mice with entirely intact polyclonal T cell repertoires to comprehensively define the mechanisms of self-tolerance.
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Article
RAS–MAPK–MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1
Many neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the muta...
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Protocol
Regulation of Ataxin-1 Phosphorylation and Its Impact on Biology
Ataxin-1 protein expression is found in the cytoplasm and nucleus of Purkinje cells, the primary site of spinocerebellar ataxia type 1 (SCA1). Phosphorylation at S776 occurs in the cytoplasm and stabilizes the...
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Chapter
Intrinsic Brain Signaling Pathways: Targets of Neuron Degeneration
Cancer and neurodegenerative disease are two of the greatest worries facing the aging population. Alteration in cell signaling pathways is a molecular process that underlies many cancers and is the targets of ...
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Article
miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis
This study demonstrates that several microRNA species co-regulate the levels of the ataxin1, a gene implicated in the development of spinocerebellar ataxia type 1 (SCA1). With ataxin1 dosage contributing to disea...
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Article
Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine-encoding repeat in ataxin 1 (ATXN1). In all known polyglutamine diseases, the glutamine ...
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Article
Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine tract in ataxin-1 (ATXN1). SCA1 pathogenesis studies support a model in which the exp...
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Article
Cut to the chase
A family of enzymes called caspases — best known for their involvement in programmed cell death — now seems to be pivotal in the progression of two neurodegenerative diseases.
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Chapter
Spinocerebellar Ataxia Type 1
Expansion of a polyglutamine repeat within the spinocerebellar ataxia type 1 (SCA1)-encoded protein, ataxin-1, causes the neurodegenerative disease, SCA1. Animal models have been generated that recapitulate ma...
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Article
Neuron protection agency
The results of an innovative way of tracing the life and death of neurons in culture favour one side of a debate about the protein accumulations associated with certain disorders of the nervous system.
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Article
RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia
The dominant polyglutamine expansion diseases, which include spinocerebellar ataxia type 1 (SCA1) and Huntington disease, are progressive, untreatable, neurodegenerative disorders. In inducible mouse models of...
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Article
A proposed mechanism of ALS fails the test in vivo
In contrast to prevailing hypotheses, a genetic study shows that the toxic gain of function associated with mutant superoxide dismutase in familial amyotropic lateral sclerosis is unlikely to be due to changes...
