Cellular and Molecular Pathways Triggering Neurodegeneration in the Spinocerebellar Ataxias

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. To date, more than 30 genes have been identified triggering the well-described clinica...

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Veröffentlicht in:Cerebellum (London, England) England), 2010-06, Vol.9 (2), p.148-166
Hauptverfasser: Matilla-Dueñas, Antoni, Sánchez, Ivelisse, Corral-Juan, Marc, Dávalos, Antoni, Alvarez, Ramiro, Latorre, Pilar
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container_issue 2
container_start_page 148
container_title Cerebellum (London, England)
container_volume 9
creator Matilla-Dueñas, Antoni
Sánchez, Ivelisse
Corral-Juan, Marc
Dávalos, Antoni
Alvarez, Ramiro
Latorre, Pilar
description The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. To date, more than 30 genes have been identified triggering the well-described clinical and pathological phenotype, but the underlying cellular and molecular events are still poorly understood. Studies of the functions of the proteins implicated in SCAs and the corresponding altered cellular pathways point to major aetiological roles for defects in transcriptional regulation, protein aggregation and clearance, alterations of calcium homeostasis, and activation of pro-apoptotic routes among others, all leading to synaptic neurotransmission deficits, spinocerebellar dysfunction, and, ultimately, neuronal demise. However, more mechanistic and detailed insights are emerging on these molecular routes. The growing understanding of how dysregulation of these pathways trigger the onset of symptoms and mediate disease progression is leading to the identification of conserved molecular targets influencing the critical pathways in pathogenesis that will serve as effective therapeutic strategies in vivo, which may prove beneficial in the treatment of SCAs. Herein, we review the latest evidence for the proposed cellular and molecular processes to the pathogenesis of dominantly inherited spinocerebellar ataxias and the ongoing therapeutic strategies.
doi_str_mv 10.1007/s12311-009-0144-2
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The growing understanding of how dysregulation of these pathways trigger the onset of symptoms and mediate disease progression is leading to the identification of conserved molecular targets influencing the critical pathways in pathogenesis that will serve as effective therapeutic strategies in vivo, which may prove beneficial in the treatment of SCAs. 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The growing understanding of how dysregulation of these pathways trigger the onset of symptoms and mediate disease progression is leading to the identification of conserved molecular targets influencing the critical pathways in pathogenesis that will serve as effective therapeutic strategies in vivo, which may prove beneficial in the treatment of SCAs. 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subjects Apoptosis - physiology
Biomedical and Life Sciences
Biomedicine
Calcium - metabolism
Cerebellum - pathology
Gene Expression Regulation - genetics
Humans
Medical research
Models, Neurological
Nerve Degeneration - etiology
Nerve Degeneration - physiopathology
Neurobiology
Neurology
Neurosciences
Pathogenesis
Peptides - toxicity
Proteins
Spinocerebellar Ataxias - complications
Spinocerebellar Ataxias - genetics
Synaptic Transmission - physiology
title Cellular and Molecular Pathways Triggering Neurodegeneration in the Spinocerebellar Ataxias
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