Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.
Cerebellum. 2013-12-05; 13(2): 269-302
DOI: 10.1007/s12311-013-0539-y
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1. Cerebellum. 2014 Apr;13(2):269-302. doi: 10.1007/s12311-013-0539-y.
Consensus paper: pathological mechanisms underlying neurodegeneration in
spinocerebellar ataxias.
Matilla-Dueñas A(1), Ashizawa T, Brice A, Magri S, McFarland KN, Pandolfo M,
Pulst SM, Riess O, Rubinsztein DC, Schmidt J, Schmidt T, Scoles DR, Stevanin G,
Taroni F, Underwood BR, Sánchez I.
Author information:
(1)Health Sciences Research Institute Germans Trias i Pujol (IGTP), Ctra. de Can
Ruti, Camí de les Escoles s/n, Badalona, Barcelona, Spain, .
Intensive scientific research devoted in the recent years to understand the
molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are
identifying new pathways and targets providing new insights and a better
understanding of the molecular pathogenesis in these diseases. In this consensus
manuscript, the authors discuss their current views on the identified molecular
processes causing or modulating the neurodegenerative phenotype in
spinocerebellar ataxias with the common opinion of translating the new knowledge
acquired into candidate targets for therapy. The following topics are discussed:
transcription dysregulation, protein aggregation, autophagy, ion channels, the
role of mitochondria, RNA toxicity, modulators of neurodegeneration and current
therapeutic approaches. Overall point of consensus includes the common vision of
neurodegeneration in SCAs as a multifactorial, progressive and reversible
process, at least in early stages. Specific points of consensus include the role
of the dysregulation of protein folding, transcription, bioenergetics, calcium
handling and eventual cell death with apoptotic features of neurons during SCA
disease progression. Unresolved questions include how the dysregulation of these
pathways triggers the onset of symptoms and mediates disease progression since
this understanding may allow effective treatments of SCAs within the window of
reversibility to prevent early neuronal damage. Common opinions also include the
need for clinical detection of early neuronal dysfunction, for more basic
research to decipher the early neurodegenerative process in SCAs in order to give
rise to new concepts for treatment strategies and for the translation of the
results to preclinical studies and, thereafter, in clinical practice.
DOI: 10.1007/s12311-013-0539-y
PMCID: PMC3943639
PMID: 24307138 [Indexed for MEDLINE]