Transplantation and Stem Cell Therapy for Cerebellar Degenerations
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Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration.
KeywordsAtaxia Cerebellum Neurotransplantation Stem cell
Supported by the Charles University Research Fund (project P36), by project CZ.1.05/2.1.00/ 03.0076 from the European Regional Development Fund and project COST No. LD12056 of the Ministry of Education, Youth and Sport of the Czech Republic. Many thanks belong to collaborators who have participated in the research.
Conflict of Interest
The author declares that he has no competing interests.
- 3.Furrer SA, Waldherr SM, Mohanachandran MS, Baughn TD, Nguyen KT, Sopher BL, et al. Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7. Hum Mol Genet. 2013;22:890–903.PubMedCentralCrossRefPubMedGoogle Scholar
- 4.Wang HL, Hu SH, Chou AH, Wang SS, Weng YH, Yeh TH. H1152 promotes the degradation of polyglutamine-expanded ataxin-3 or ataxin-7 independently of its ROCK-inhibiting effect and ameliorates mutant ataxin-3-induced neurodegeneration in the SCA3 transgenic mouse. Neuropharmacology. 2013;70:1–11.CrossRefPubMedGoogle Scholar