BIOMAT Database Logo BIOMAT Database Logo

Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. 2010

Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.

Spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by progressive cerebellar ataxia and dysarthria. We have identified missense mutations in prodynorphin (PDYN) that cause SCA23 in four Dutch families displaying progressive gait and limb ataxia. PDYN is the precursor protein for the opioid neuropeptides, α-neoendorphin, and dynorphins A and B (Dyn A and B). Dynorphins regulate pain processing and modulate the rewarding effects of addictive substances. Three mutations were located in Dyn A, a peptide with both opioid activities and nonopioid neurodegenerative actions. Two of these mutations resulted in excessive generation of Dyn A in a cellular model system. In addition, two of the mutant Dyn A peptides induced toxicity above that of wild-type Dyn A in cultured striatal neurons. The fourth mutation was located in the nonopioid PDYN domain and was associated with altered expression of components of the opioid and glutamate system, as evident from analysis of SCA23 autopsy tissue. Thus, alterations in Dyn A activities and/or impairment of secretory pathways by mutant PDYN may lead to glutamate neurotoxicity, which underlies Purkinje cell degeneration and ataxia. PDYN mutations are identified in a small subset of ataxia families, indicating that SCA23 is an infrequent SCA type (∼0.5%) in the Netherlands and suggesting further genetic SCA heterogeneity.

UI MeSH Term Description Entries
D008297 Male Males
D010375 Pedigree The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition. Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D011498 Protein Precursors Precursors, Protein
D011689 Purkinje Cells The output neurons of the cerebellar cortex. Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D004399 Dynorphins A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters. Dynorphin,Dynorphin (1-17),Dynorphin A,Dynorphin A (1-17)
D004745 Enkephalins One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. Enkephalin
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013132 Spinocerebellar Degenerations A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked. Ataxias, Hereditary,Cerebellar Ataxia, Early Onset,Cerebellar Ataxia, Late Onset,Cerebellar Degenerations, Primary,Corticostriatal-Spinal Degeneration,Marie Cerebellar Ataxia,Marinesco-Sjogren Syndrome,Spinocerebellar Degeneration,Early Onset Cerebellar Ataxia,Familial Spinocerebellar Degenerations,Garland-Moorhouse Syndrome,Hereditary Oligophrenic Cerebello-Lental Degeneration,Hereditary Spinocerebellar Degenerations,Inherited Spinocerebellar Degenerations,Late Onset Cerebellar Ataxia,Marie's Cerebellar Ataxia,Marinesco-Garland Syndrome,Marinesco-Sjogren Syndrome-Hypergonadotrophic Hypogonadism,Marinesco-Sjogren Syndrome-Myopathy,Marinesco-Sjogren-Garland Syndrome,Marinesco-Sjögren Syndrome,Spino Cerebellar Degenerations,Spino-Cerebellar Degenerations,Spinocerebellar Diseases,Ataxia, Hereditary,Cerebellar Ataxia, Marie,Cerebellar Ataxia, Marie's,Cerebellar Degeneration, Primary,Corticostriatal Spinal Degeneration,Corticostriatal-Spinal Degenerations,Degeneration, Corticostriatal-Spinal,Degeneration, Familial Spinocerebellar,Degeneration, Hereditary Spinocerebellar,Degeneration, Inherited Spinocerebellar,Degeneration, Primary Cerebellar,Degeneration, Spino Cerebellar,Degeneration, Spino-Cerebellar,Degeneration, Spinocerebellar,Degenerations, Corticostriatal-Spinal,Degenerations, Familial Spinocerebellar,Degenerations, Hereditary Spinocerebellar,Degenerations, Inherited Spinocerebellar,Degenerations, Primary Cerebellar,Degenerations, Spino Cerebellar,Degenerations, Spinocerebellar,Familial Spinocerebellar Degeneration,Garland Moorhouse Syndrome,Hereditary Ataxia,Hereditary Ataxias,Hereditary Oligophrenic Cerebello Lental Degeneration,Hereditary Spinocerebellar Degeneration,Hypogonadism, Marinesco-Sjogren Syndrome-Hypergonadotrophic,Inherited Spinocerebellar Degeneration,Marinesco Garland Syndrome,Marinesco Sjogren Garland Syndrome,Marinesco Sjogren Syndrome,Marinesco Sjogren Syndrome Hypergonadotrophic Hypogonadism,Marinesco Sjogren Syndrome Myopathy,Marinesco Sjögren Syndrome,Primary Cerebellar Degeneration,Primary Cerebellar Degenerations,Spino Cerebellar Degeneration,Spino-Cerebellar Degeneration,Spinocerebellar Degeneration, Familial,Spinocerebellar Degeneration, Hereditary,Spinocerebellar Degeneration, Inherited,Spinocerebellar Degenerations, Familial,Spinocerebellar Degenerations, Hereditary,Spinocerebellar Degenerations, Inherited,Spinocerebellar Disease,Syndrome, Garland-Moorhouse,Syndrome, Marinesco-Garland,Syndrome, Marinesco-Sjogren,Syndrome, Marinesco-Sjogren-Garland,Syndrome, Marinesco-Sjögren,Syndrome-Hypergonadotrophic Hypogonadism, Marinesco-Sjogren,Syndrome-Myopathy, Marinesco-Sjogren

Related Publications

Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23.
March 2021, Brain pathology (Zurich, Switzerland),
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Spectrin mutations cause spinocerebellar ataxia type 5.
February 2006, Nature genetics,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Mutations in KCND3 cause spinocerebellar ataxia type 22.
December 2012, Annals of neurology,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Spinocerebellar ataxia type 7: a neurodegenerative disorder with peripheral neuropathy.
January 2015, European neurology,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44.
November 2017, American journal of human genetics,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44.
October 2017, American journal of human genetics,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44.
September 2017, American journal of human genetics,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
ELOVL5 mutations cause spinocerebellar ataxia 38.
August 2014, American journal of human genetics,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19.
December 2012, Annals of neurology,
Georgy Bakalkin, and Hiroyuki Watanabe, and Justyna Jezierska, and Cloë Depoorter, and Corien Verschuuren-Bemelmans, and Igor Bazov, and Konstantin A Artemenko, and Tatjana Yakovleva, and Dennis Dooijes, and Bart P C Van de Warrenburg, and Roman A Zubarev, and Berry Kremer, and Pamela E Knapp, and Kurt F Hauser, and Cisca Wijmenga, and Fred Nyberg, and Richard J Sinke, and Dineke S Verbeek
Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions.
May 1998, Human molecular genetics,
Copied contents to your clipboard!