About
14
Publications
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327
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Introduction
Additional affiliations
September 2016 - present
March 2012 - present
Position
- PhD Student
Description
- Identifying novel mutations causing spinocerebellar ataxia, and unraveling the underlying molecular mechanism of specific SCA types, namely SCA19 and SCA23.
March 2012 - February 2016
Publications
Publications (14)
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease characterized by progressive ataxia and degeneration of specific neuronal populations, including Purkinje cells (PCs) in the cerebellum. Previous studies have demonstrated a critical role for various evolutionarily conserved signaling pathways in cerebellar pat...
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease characterized by progressive ataxia and degeneration of specific neuronal populations, including Purkinje cells (PCs) in the cerebellum. Previous studies have demonstrated a critical role for various evolutionarily conserved signaling pathways in cerebellar pat...
Spinocerebellar ataxia type 23 (SCA23) is a late‐onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by pathogenic variants in PDYN, which encodes prodynorphin (PDYN). PDYN is processed into the opioid peptides α‐neoendorphin and dynorphins (Dyn) A and B; i...
Background
Spinocerebellar ataxia type 23 (SCA23) is a late-onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by mutations in PDYN, which encodes the opioid precursor protein prodynorphin (PDYN). PDYN is processed into the opioid peptides α-neoendorphin,...
The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias in genetic nomenclature, are a rare group of progressive neurodegenerative disorders characterized by loss of balance and coordination. Despite the identification of numerous disease genes, a substantial number of cases still remain without a genetic diagnosis. Here,...
Spinocerebellar ataxia type 23 (SCA23) is caused by missense mutations in prodynorphin (PDYN), encoding the precursor protein for the opioid neuropeptides α-neoendorphin, Dynorphin (Dyn) A, and Dyn B, leading to neurotoxic
elevated mutant Dyn A levels. Dyn A acts on opioid receptors to reduce pain in the spinal cord, but its cerebellar function
rem...
Sir,
With the introduction of next generation sequencing into research and the clinic, geneticists now face the problem of variant interpretation in single cases, which is a challenging task due to the lack of data from additional affected family members. For the majority of the variants in our genome we do not know whether they are damaging and p...
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Spinocerebellar ataxia type 23 is caused by mutations in PDYN, which encodes the opioid neuropeptide precursor protein, prodynorphin. Smeets et al. generate the first mouse model of SCA23, and reveal elevated levels of mutant dynorphin A, associated with climbing fiber retraction, Purkinje cell death and altered opioid and...
The dominantly inherited cerebellar ataxias are a heterogeneous group of neurodegenerative disorders caused by Purkinje cell loss in the cerebellum. Recently, we identified loss-of-function mutations in the KCND3 gene as the cause of spinocerebellar ataxia type 19/22 (SCA19/22), revealing a previously unknown role for the voltage-gated potassium ch...
Author Summary
Huntington’s disease (HD) is a neurodegenerative disorder in which the mutation results in an extra-long tract of glutamines that causes the huntingtin protein to aggregate. It is characterized by neurological symptoms and brain pathology, which is associated with nuclear and cytoplasmic protein aggregates and with transcriptional de...
Cerebellar ataxias are progressive neurodegenerative disorders characterized by atrophy of the cerebellum leading to motor dysfunction, balance problems, and limb and gait ataxia. These include amongst others the dominantly inherited spinocerebellar ataxias, recessive cerebellar ataxias such as Friedreich's ataxia, and X-linked cerebellar ataxias....
Cerebellar ataxias are progressive neurodegenerative disorders characterized by atrophy of the cerebellum leading to motor dysfunction, balance problems, and limb and gait ataxia. These include amongst others the dominantly inherited spinocerebellar ataxias, recessive cerebellar ataxias such as Friedreich’s ataxia, and X-linked cerebellar ataxias....
