Mutant Ataxin-3-Containing Aggregates (MATAGGs) in Spinocerebellar Ataxia Type 3: Dynamics of the Disorder.

Spinocerebellar ataxia type 3 (SCA3) is the most common type of SCA worldwide caused by abnormal polyglutamine expansion in the coding region of the ataxin-3 gene. Ataxin-3 is a multi-faceted protein involved in various cellular processes such as deubiquitination, cytoskeletal organisation, and transcriptional regulation. The presence of an expanded poly(Q) stretch leads to altered processing and misfolding of the protein culminating in the production of insoluble protein aggregates in the cell.

Tissue-Specific Upregulation of Drosophila Insulin Receptor (InR) Mitigates Poly(Q)-Mediated Neurotoxicity by Restoration of Cellular Transcription Machinery.

Polyglutamine [poly(Q)] disorders are a class of trinucleotide repeat expansion neurodegenerative disorders which are dominantly inherited and progressively acquired with age. This group of disorders entail the characteristic formation of protein aggregates leading to widespread loss of neurons in different regions of the brain. SCA3 and HD, the two most commonly occurring types of poly(Q) disorders were examined in the present study.

Cell cycle-dependent regulation of cytoglobin by Skp2.

Cytoglobin (Cygb) is a cellular haemoprotein belonging to the globin family with ambiguous biological functions. Downregulation of Cygb in many cancers is indicative of its tumour-suppressive role. This is the first report showing the cell cycle regulation of Cygb, which was found to peak at G1 and rapidly decline in S phase.

Transactivation Domain of Human c-Myc Is Essential to Alleviate Poly(Q)-Mediated Neurotoxicity in Drosophila Disease Models.

Polyglutamine (poly(Q)) disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, represent a group of neurological disorders which arise due to an atypically expanded poly(Q) tract in the coding region of the affected gene. Pathogenesis of these disorders inside the cells begins with the assembly of these mutant proteins in the form of insoluble inclusion bodies (IBs), which progressively sequester several vital cellular transcription factors and other essential proteins, and finally leads to neuronal dysfunction and apoptosis. We have shown earlier that targeted upregulation of Drosophila myc (dmyc) dominantly suppresses the poly(Q) toxicity in Drosophila.

Drosophila Myc, a novel modifier suppresses the poly(Q) toxicity by modulating the level of CREB binding protein and histone acetylation.

Polyglutamine or poly(Q) disorders are dominantly inherited neurodegenerative diseases characterised by progressive loss of neurons in cerebellum, basal ganglia and cortex in adult human brain. Overexpression of human form of mutant SCA3 protein with 78 poly(Q) repeats leads to the formation of inclusion bodies and increases the cellular toxicity in Drosophila eye. The present study was directed to identify a genetic modifier of poly(Q) diseases that could be utilised as a potential drug target.