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Calretinin interacts with huntingtin and reduces mutant huntingtin‐caused cytotoxicity

pmid: 22891683
Calretinin interacts with huntingtin and reduces mutant huntingtin‐caused cytotoxicity
AbstractHuntington's disease (HD) is a devastating neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats encoding for polyglutamine (polyQ) in the huntingtin (Htt) gene. Despite considerable effort, the mechanisms underlying the toxicity of the mutated Htt protein remains largely uncertain. To identify novel therapeutic targets, we recently employed the approach of tandem affinity purification and discovered that calretinin (Cr), a member of the EF‐hand family of calcium‐binding proteins, is preferentially associated with mHtt, although it also interacts with wild‐type Htt. These observations were supported by coimmunoprecipitation and by colocalization of Cr with mHtt in neuronal cultures. Over‐ expression of Cr reduced mHtt‐caused cytotoxicity in both non‐neuronal and neuronal cell models of HD, whereas knockdown of Cr expression in the cells enhanced mHtt‐caused neuronal cell death. In addition, over‐expression of Cr was also associated with reduction of intracellular free calcium and activation of Akt. These results suggest that Cr may be a potential therapeutic target for treatment of HD.
- University of Tübingen Germany
- Helmholtz Zentrum München Germany
- Protein Sciences United States
- Mount Marty College United States
- University of South Dakota United States
Male, Huntingtin Protein, Calcium-Binding Proteins, Primary Cell Culture, Down-Regulation, Nuclear Proteins, Nerve Tissue Proteins, Disease Models, Animal, Mice, Mice, Neurologic Mutants, HEK293 Cells, Huntington Disease, S100 Calcium Binding Protein G, Calbindin 2, Gene Knockdown Techniques, Nerve Degeneration, Animals, Humans, Female
Male, Huntingtin Protein, Calcium-Binding Proteins, Primary Cell Culture, Down-Regulation, Nuclear Proteins, Nerve Tissue Proteins, Disease Models, Animal, Mice, Mice, Neurologic Mutants, HEK293 Cells, Huntington Disease, S100 Calcium Binding Protein G, Calbindin 2, Gene Knockdown Techniques, Nerve Degeneration, Animals, Humans, Female
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